Scottish Fold cats (Felis catus, Linnaeus 1758) are one of the most well-known and popular cat breeds in the world, characterized by their folded ears attached to the head. Very frequently, cats fall prey of different trauma and accidents that can cause bone fractures especially in the metapodial bones. The method of radiometry is used in veterinary practice to visualize and measure different parts of the animal skeleton. The aim of this study was to assess the linear parameters derived from radiographic images of the metacarpals and metatarsals in Scottish Fold cats and additionally detecting potential sexual dimorphism. Radiographic images of 24 adult Scottish Fold cats (12 male and 12 females) of different ages and weights were analysed. Six linear measurements of the metapodial bones were evaluated to investigate any differences between the sexes. The linear radiometric measurements of the five metacarpals (MC1-5) and the four metatarsals (MT2-5) bones were larger in male metapodial bones than that of female cats. The maximum length (Ml) of the MC1 and MC2 was statistically different between sex, respectively, (p = 0.001) and (p = 0.05). The others metacarpal bones were different in mostly all linear parameters but not statistically significant. The most significant differences between sexes were observed in the parameter of width proximal end (Wp) of MC1-3 (p = 0.001) and MC4 (p = 0.05). More statistical different was MT2 and less MT3. The linear parameter of Bd of the MT4 was the most different statistically between sex (p = 0.001). The results of the study will be useful in function of comparative anatomy, in veterinary clinical practice, in zoo archaeology and in the veterinary forensic investigation.

Members of the subfamily Heterocongrinae (Congridae) are a peculiar group of anguilliform eels that construct sandy borrows, form large colonies, and are popularly recognized as garden eels. They live with most of their bodies inside self-constructed borrows exposing their heads and trunk to feed on zooplankton, preferably copepods, that are brought passively by currents. As plankton feeders there was a suspicion that their branchial skeleton would have structures that could aid in the filtering process, such as highly developed or modified branchial rakers, which are observed in other suspension-feeding fishes, such as anchovies and sardines. Branchial rakers, however, were considered to be absent across Anguilliformes (except for Protanguilla). Nonetheless, specimens that were examined using clearing and staining and computed tomography showed, in all cases, branchial rakers associated with their gill arches. Heterocongrines have branchial rakers across their first to fourth branchial arches. These rakers are conical and apparently unossified, but further studies are necessary to attest its degree of ossification or its complete absence. Their pharyngeal tooth plates are reduced, a condition that may reflect their preference for smaller food items. Additionally, they may use crossflow filtering to feed, although detailed studies are necessary to clarify if hydrosol sieving may also aid in food capture. Furthermore, the present study proposes that the presence of branchial rakers should be better investigated in Anguilliformes with similar feeding habits as heterocongrines, considering that these structures may be more widespread within the group than previously considered.

The development of the sea urchin larval body plan is well understood from extensive studies of embryonic patterning. However, fewer studies have investigated the late larval stages during which the unique pentaradial adult body plan develops. Previous work on late larval development highlights major tissue changes leading up to metamorphosis, but the location of specific cell types during juvenile development is less understood. Here, we improve on technical limitations by applying highly sensitive hybridization chain reaction fluorescent in situ hybridization (HCR-FISH) to the fast-developing and transparent sea urchin Lytechinus pictus, with a focus on skeletogenic cells. First, we show that HCR-FISH can be used in L. pictus to precisely localize skeletogenic cells in the rudiment. In doing so, we provide a detailed staging scheme for the appearance of skeletogenic cells around the rudiment prior to and during biomineralization and show that many skeletogenic cells unassociated with larval rods localize outside of the rudiment prior to localizing inside. Second, we show that downstream biomineralization genes have similar expression patterns during larval and juvenile skeletogenesis, suggesting some conservation of skeletogenic mechanisms during development between stages. Third, we find co-expression of blastocoelar and skeletogenic cell markers around juvenile skeleton located outside of the rudiment, which is consistent with data showing that cells from the non-skeletogenic mesoderm embryonic lineage contribute to the juvenile skeletogenic cell lineage. This work sets the foundation for subsequent studies of other cell types in the late larva of L. pictus to better understand juvenile body plan development, patterning, and evolution.

OBJECTIVE: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan.
METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant.
RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before.
CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.

A hydrostatic skeleton allows a soft body to transmit muscular force via internal pressure. A human\'s tongue, an octopus\' arm and a nematode\'s body illustrate the pervasive presence of hydrostatic skeletons among animals, which has inspired the design of soft engineered actuators. However, there is a need for a theoretical basis for understanding how hydrostatic skeletons apply mechanical work. We therefore modeled the shape change and mechanics of natural and engineered hydrostatic skeletons to determine their mechanical advantage (MA) and displacement advantage (DA). These models apply to a variety of biological structures, but we explicitly consider the tube feet of a sea star and the body segments of an earthworm, and contrast them with a hydraulic press and a McKibben actuator. A helical winding of stiff, elastic fibers around these soft actuators plays a critical role in their mechanics by maintaining a cylindrical shape, distributing forces throughout the structure and storing elastic energy. In contrast to a single-joint lever system, soft hydrostats exhibit variable gearing with changes in MA generated by deformation in the skeleton. We found that this gearing is affected by the transmission efficiency of mechanical work (MA×DA) or, equivalently, the ratio of output to input work. The transmission efficiency changes with the capacity to store elastic energy within helically wrapped fibers or associated musculature. This modeling offers a conceptual basis for understanding the relationship between the morphology of hydrostatic skeletons and their mechanical performance.

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

BACKGROUND: Mammalian skeletons are largely formed before birth. Heterochronic changes in skeletal formation can be investigated by comparing the order of ossification for different elements of the skeleton. Due to the challenge of collecting prenatal specimens in viviparous taxa, opportunistically collected museum specimens provide the best material for studying prenatal skeletal development across many mammalian species. Previous studies have investigated ossification sequence in a range of mammalian species, but little is known about the pattern of bone formation in Carnivora. Carnivorans have diverse ecologies, diets, and biomechanical specializations and are well-suited for investigating questions in evolutionary biology. Currently, developmental data on carnivorans is largely limited to domesticated species. To expand available data on carnivoran skeletal development, we used micro-computed tomography (micro-CT) to non-invasively evaluate the degree of ossification in all prenatal carnivoran specimens housed in the Harvard Museum of Comparative Zoology. By coding the presence or absence of bones in each specimen, we constructed ossification sequences for each species. Parsimov-based genetic inference (PGi) was then used to identify heterochronic shifts between carnivoran lineages and reconstruct the ancestral ossification sequence of Carnivora.
RESULTS: We used micro-CT to study prenatal ossification sequence in six carnivora species: Eumetopias jubatus (Steller sea lion, n = 6), Herpestes javanicus (small Indian mongoose, n = 1), Panthera leo (lion, n = 1), Urocyon cinereoargenteus (gray fox, n = 1), Ursus arctos arctos (Eurasian brown bear, n = 1), and Viverricula indica (small Indian civet, n = 5). Due to the relatively later stage of collection for the available specimens, few heterochronic shifts were identified. Ossification sequences of feliform species showed complete agreement with the domestic cat. In caniforms, the bear and fox ossification sequences largely matched the dog, but numerous heterochronic shifts were identified in the sea lion.
CONCLUSIONS: We use museum specimens to generate cranial and postcranial micro-CT data on six species split between the two major carnivoran clades: Caniformia and Feliformia. Our data suggest that the ossification sequence of domestic dogs and cats are likely good models for terrestrial caniforms and feliforms, respectively, but not pinnipeds.

The emergence of Homo sapiens in Eastern Asia is a topic of significant research interest. However, well-preserved human fossils in secure, dateable contexts in this region are extremely rare, and often the subject of intense debate owing to stratigraphic and geochronological problems. Tongtianyan cave, in Liujiang District of Liuzhou City, southern China is one of the most important fossils finds of H. sapiens, though its age has been debated, with chronometric dates ranging from the late Middle Pleistocene to the early Late Pleistocene. Here we provide new age estimates and revised provenience information for the Liujiang human fossils, which represent one of the most complete fossil skeletons of H. sapiens in China. U-series dating on the human fossils and radiocarbon and optically stimulated luminescence dating on the fossil-bearing sediments provided ages ranging from ~33,000 to 23,000 years ago (ka). The revised age estimates correspond with the dates of other human fossils in northern China, at Tianyuan Cave (~40.8-38.1 ka) and Zhoukoudian Upper Cave (39.0-36.3 ka), indicating the geographically widespread presence of H. sapiens across Eastern Asia in the Late Pleistocene, which is significant for better understanding human dispersals and adaptations in the region.

OBJECTIVE: The Sanders Scoring System has revolutionized the way we assess the remaining growth potential of the skeleton. However, because it involves radiation exposure, it must be used with caution in children. The purpose of the study was to evaluate whether the Sanders skeletal maturity score (SMS) could be accurately determined using ultrasound (U).
METHODS: We took radiographs (R) of the hand and performed U of the thumb and index finger in 115 patients between six and 19 years of age who were undergoing treatment for scoliosis or limb deformities. Paediatric orthopaedic surgeons, a paediatrician, and a paediatric radiologist were evaluated the blinded images. Those classified images are based on the SMS and the Thumb Ossification Composite Index (TOCI).
RESULTS: Intrarater reliability was high for SMS and slightly weaker for TOCI, but still significant. Interrater reliability was clear for R and weaker for U in both staging systems. Ultimately, SMS 3 and 7 achieved the highest percentage of concordance (P) of 71.7% and 66.0%, respectively, when U was performed. Combining the clinically relevant groups of SMS 3&4 and SMS 7&8 also significantly increased peak scores (SMS 3 and 4 P = 76.7%; SMS 7 and 8 P = 79.7%). The probabilities of peak scores were significantly weaker when the TOCI score was examined.
CONCLUSIONS: Our study shows that U can be used effectively especially to measure stages 3 and 4 and stages 7 and 8 of SMS. The U method is easy to use and therefore may offer advantages in clinical practice without the need for radiation exposure.

Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,β-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans.