Compressive and tensile mechanical properties of the porcine nasal septum

The expanding nasal septal cartilage is believed to create a force that powers midfacial growth. In addition, the nasal septum is postulated to act as a mechanical strut that prevents the structural collapse of the face under masticatory loads. Both roles imply that the septum is subject to complex biomechanical loads during growth and mastication. The purpose of this study was to measure the mechanical properties of the nasal septum to determine (1) whether the cartilage is mechanically capable of playing an active role in midfacial growth and in maintaining facial structural integrity and (2) if regional variation in mechanical properties is present that could support any of the postulated loading regimens. Porcine septal samples were loaded along the horizontal or vertical axes in compression and tension, using different loading rates that approximate the in vivo situation. Samples were loaded in random order to predefined strain points (2–10%) and strain was held for 30 or 120 seconds while relaxation stress was measured. Subsequently, samples were loaded until failure. Stiffness, relaxation stress and ultimate stress and strain were recorded. Results showed that the septum was stiffer, stronger and displayed a greater drop in relaxation stress in compression compared to tension. Under compression, the septum displayed non-linear behavior with greater stiffness and stress relaxation under faster loading rates and higher strain levels. Under tension, stiffness was not affected by strain level. Although regional variation was present, it did not strongly support any of the suggested loading patterns. Overall, results suggest that the septum might be mechanically capable of playing an active role in midfacial growth as evidenced by increased compressive residual stress with decreased loading rates. However, the low stiffness of the septum compared to surrounding bone does not support a strut role. The relatively low stiffness combined with high stress relaxation under fast loading rates suggests that the nasal septum is a stress dampener, helping to absorb and dissipate loads generated during mastication.     

Evidence for diet partitioning among three coexisting native freshwater fishes in South Africa's Cape Fold Ecoregion

The partitioning of limited resources commonly explains how different species can coexist within the same ecological community. In this 2010 study, the diets of three coexisting freshwater fishes (Cape galaxias Galaxias zebratus, n = 27; Cape kurper Sandelia capensis, n = 60; Breede River redfin Pseudobarbus burchelli, n = 77) were characterised and compared in three headwater streams in South Africa's Cape Fold Ecoregion using gut contents and stable isotope analyses. These data were analysed to ascertain whether the three species exploit distinct trophic niches. Both approaches provided evidence that these species occupy different trophic niches, though with some overlap. However, dietary differences among sites were not consistent and were probably influenced by site-specific factors like resource availability. Pseudobarbus burchelli had a broader niche breadth at Tierkloof Stream than the other two species, but not at Waaihoek or Tierstel Streams. Our results also suggest that P. burchelli consumed a more omnivorous diet than do the other two species, whereas S. capensis occupied a higher trophic position than the other two species and consumed vertebrates. Our findings suggest that these species occupy non-equivalent feeding niches in Cape Fold Ecoregion headwater streams, and that diet partitioning might facilitate their coexistence in these systems.     

The KRAS-regulated kinome identifies WEE1 and ERK coinhibition as a potential therapeutic strategy in KRAS-mutant pancreatic cancer

Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile of the KRAS-regulated kinase signaling network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). We knocked down KRAS expression in a panel of six cell lines and then applied multiplexed inhibitor bead/MS to monitor changes in kinase activity and/or expression. We hypothesized that depletion of KRAS would result in downregulation of kinases required for KRAS-mediated transformation and in upregulation of other kinases that could potentially compensate for the deleterious consequences of the loss of KRAS. We identified 15 upregulated and 13 downregulated kinases in common across the panel of cell lines. In agreement with our hypothesis, all 15 of the upregulated kinases have established roles as cancer drivers (e.g., SRC, TGF-β1, ILK), and pharmacological inhibition of one of these upregulated kinases, DDR1, suppressed PDAC growth. Interestingly, 11 of the 13 downregulated kinases have established driver roles in cell cycle progression, particularly in mitosis (e.g., WEE1, Aurora A, PLK1). Consistent with a crucial role for the downregulated kinases in promoting KRAS-driven proliferation, we found that pharmacological inhibition of WEE1 also suppressed PDAC growth. The unexpected paradoxical activation of ERK upon WEE1 inhibition led us to inhibit both WEE1 and ERK concurrently, which caused further potent growth suppression and enhanced apoptotic death compared with WEE1 inhibition alone. We conclude that system-wide delineation of the KRAS-regulated kinome can identify potential therapeutic targets for KRAS-mutant pancreatic cancer.     

Compressive loading on bone surfaces from muscular contraction: an in vivo study in the miniature pig,Sus scrofa

Several authors have speculated that muscles contracting adjacent to bony surfaces may cause compressive loads against the bone and thus influence skull development. This study was undertaken to evaluate the premise of this argument. A flat, semiconductor pressure transducer was surgically placed on bony surfaces beneath muscle attachments. Pressures were recorded during normal mastication (n = 7) and while overlying muscles were stimulated in anesthetized pigs (n = 15). The transducer was highly specific; no pressure was recorded in quiescent or passively stretched muscles or when other muscles were stimulated. Contraction of the overlying muscles exerted high normal loads on the bone, always exceeding systolic blood pressure (16 kPa). Temporal fossa pressure during mastication followed temporalis electromyographic (EMG) signals with a lag period approximating the twitch contraction time. When three different sites were compared in anesthetized animals, compressive load was highest on the temporal fossa (111.4 ± 56.5 kPa, n = 15), intermediate on the mandibular angle (58.4 ± 28.3 kPa, n = 4), and lowest on the medial side of the zygomatic arch (37.2 ± 19.7 kPa, n = 15). Pressure amplitudes were not related to body size or relative muscle size. Muscle complexity and compartmental constraints did appear to influence pressure. Disruption of the external aponeurosis of the masseter decreased pressure on the mandibular angle by 45%, confirming the importance of tendinous constraint in determining pressure production. Thus, contracting muscles exert substantial but site-specific compressive loads on adjacent bone surfaces. J. Morphol. 238:71–80, 1998. © 1998 Wiley-Liss, Inc.     

Movement of the epiglottis in mammals

In contrast to adult humans, the epiglottis of other mammals and infant humans is situated close to the soft palate. It has been argued that this posture is maintained during swallowing, with food passing laterally around an intact airway. To test this supposition, the movement of the epiglottis in two contrasting mammalian species, pigs and ferrets, was studied by placing radiopaque markers on the epiglottis and soft palate. Swallowing was observed with videofluoroscopy while the animals were feeding on hard and soft foods, liquids, and food mixed with barium sulfate. Analysis of the images showed that bolus formation and downward movement of the epiglottis away from the soft palate were unvarying phenomena in both animals for all tested foods. The duration of the epiglottic movement was approximately 0.3 s for liquids and slightly longer for solids. Because swallowing never occurred past an upright epiglottis, the results of this study do not support the hypothesis that adult animals maintain a patent airway during swallowing. Instead, the epiglottis in nonhuman mammals downfolds similarly to that of adult humans during swallowing. © 1996 Wiley-Liss, Inc.     

The ecological integrity of the lower Olifants River,Limpopo province,South Africa: 2009–2015 – Part B: Tributaries of the Olifants River

Monitoring on the Lowveld reaches of the Olifants River, Limpopo River System, and its Steelpoort, Blyde, Klaserie and Selati tributaries was initiated in 2009. Analysis of the 2009–2015 data from four Olifants River sites showed deterioration in the river’s ecological condition between where it enters the Lowveld and where it enters the Kruger National Park, with a slight recovery within the Kruger National Park. Physico-chemical, aquatic macroinvertebrate and fish data collected in 2009–2015 at six sites on the Steelpoort, Blyde, Klaserie and Selati tributaries of the Olifants River corroborated the ecological condition of these tributaries. The Selati was the most polluted and was in a critically modified condition, whereas the Klaserie and Steelpoort were in fair condition and the Blyde was in good condition. The Selati appeared to have a significant negative impact on the water quality, macroinvertebrates and fish of the Olifants River within the Kruger National Park.