Skeletal Morphology Research Articles

Site Formation Histories and Context of Human Occupations at the Paleolithic Site of La Ferrassie (Dordogne, France)

The Paleolithic site of La Ferrassie (Dordogne, France) has contributed significantly to the understanding of Middle and Upper Paleolithic technocomplexes, as well as Neanderthal skeletal morphology. Excavations at the site have spanned more than a century and uncovered rich archaeological assemblages associated with the Mousterian, Châtelperronian, Aurignacian and Gravettian technocomplexes. Renewed excavations exposed a sequence spanning both Middle and Upper Paleolithic occupations in the Western Sector and low-density Mousterian deposits and Châtelperronian in the Northern Sector. Here, we report on an extensive geoarchaeological study of deposits at the western end of the site to reconstruct and interpret both the depositional history of the sediments and associated human occupations in this poorly documented part of La Ferrassie. Our results point to the nature of the site as originally a karstic cave, with the Western Sector located in what would have been the cave’s mouth. The stratigraphic sequence comprises first fluvial deposition (Phase I) followed by soliflucted deposits and accretion cones that emanate from an elevated platform situated several meters above the modern road next to the site (Phase II) and, finally, spatially restricted channeling (Phase III). Most archaeological assemblages are associated with Phase II and reflect an interplay between occupations directly in this area and bones and artifacts sliding down the slope from the upper platform. Unlike in the Western Sector, in the Northern Sector — situated along the north wall and several meters inside the footprint of the cave — cold features dominate the entirety of the sequence; we interpret these as being linked to microenvironments specific to this location of the karst rather than to general (external) climatic conditions. Relevant is the identification of patterned ground formation in this area, which can be clearly linked to the “monticule” features first reported by Capitan and Peyrony and erroneously interpreted as anthropogenic in origin. Our geoarchaeological results point to a large and complex karst system, with distinct depositional sources and often locally independent sedimentary histories throughout its extent. These formation pathways have differently impacted the main occupation areas and resulted in distinct degrees of preservation of the archaeological assemblages throughout the different areas of the site.

Effects of Myostatin b Knockout on Offspring Body Length and Skeleton in Yellow Catfish (Pelteobagrus fulvidraco).

Based on obtaining mstnb gene knockout in Pelteobagrus fulvidraco, a study on the effect of the mstn gene on skeletal morphology and growth was performed by comparing the number and length of the vertebrae of mutant and wild-type fish in a sibling group of P. fulvidraco, combined with the differences in cells at the level of vertebral skeletal tissue. It was found that mstnb gene knockdown resulted in a reduction in the number of vertebrae, the length, and the intervertebral distance in P. fulvidraco, and these changes may be the underlying cause of the shorter body length in mutant P. fulvidraco. Further, histological comparison of the same sites in the mstn mutant and wild groups of P. fulvidraco also revealed that the number and density of osteocytes were greater in mstnb knockout P. fulvidraco than in wild-type P. fulvidraco. Our results demonstrated that when using genome editing technology to breed new lines, the effects of knockout need to be analyzed comprehensively and may have some unexpected effects due to insufficient study of the function of certain genes.

CUDC‑101 is a potential target inhibitor for the EGFR‑overexpression bladder cancer cells.

Bladder cancer is one of the most common urological malignancies worldwide. The molecular mechanism underlying its development is complex, but its carcinogenesis has been proposed to occur with cell proliferation and resistance to apoptosis, driven by the signaling activity of abundant EGFR and receptor tyrosine‑protein kinase erbB‑2. In the present study, T24 bladder cancer cell lines with EGFR‑overexpression were constructed, before the multi‑target inhibitor CUDC‑101 was used to investigate its potential as a targeted therapeutic agent for bladder cancer using chemosensitivity methods. The results showed that CUDC‑101 induced cytotoxic effects, inhibited growth vitality and proliferation in a dose‑dependent manner. CUDC‑101 also altered the skeletal morphology and microfilament structure, while blocking cell cycle progression and causing apoptosis. These results supported the proposed cytotoxic effects of CUDC‑101, in addition to its inhibitory effects on cell division and proliferation in EGFR‑overexpressing bladder cancer cells. Therefore CUDC‑101 may to be a potential therapeutic option for the treatment of bladder cancer.

Mapping sexual dimorphism signal in the human cranium

The study of sexual dimorphism in human crania has important applications in the fields of human evolution and human osteology. Current, the identification of sex from cranial morphology relies on manual visual inspection of identifiable anatomical features, which can lead to bias due to user’s expertise. We developed a landmark-based approach to automatically map the sexual dimorphism signal on the human cranium. We used a sex-known sample of 228 individuals from different geographical locations to identify which cranial regions are most sexually dimorphic taking into account shape, form and size. Our results, which align with standard protocols, show that glabellar and supraciliary regions, the mastoid process and the nasal region are the most sexually dimorphic traits (with an accuracy of 73%). The accuracy increased to 77% if they were considered together. Surprisingly the occipital external protuberance resulted to be not sexually dimorphic but mainly related to variations in size. Our approach here applied could be expanded to map other variable signals on skeletal morphology.

Osteogenic properties of bioactive titanium in inflammatory environment.

It is very important that the effects of surface modified titanium on osteogenic differentiation of bone marrow mesenchymal stem cells in the process of bone regeneration. The bio-function of modified titanium could be affected by the inflammatory micro-environment. The aim of this study was to investigate the effects of modified titanium on osteogenic differentiation in the inflammatory conditions and the osteogenic properties of the modified titanium dental implant in vivo. The medical pure titanium metals (PT-Ti) subjected to Anodic Oxidation (AO-Ti), Sand Blasting/acid etching (SLA-Ti) and Plasma-sprayed HA coating (HA coating-Ti) were used for regulating the osteogenic properties of MSCs in the normal and inflammatory conditions. The amount of the MSCs in the inflammatory environment were more similar to that in the non-inflammatory environment after cultured on AO-Ti samples for 7D. However, the proliferation of the MSCs was obviously inhibited on the other groups in the inflammatory condition. The morphology of MSC cells on the modified titanium surface was affected in the inflammatory conditions and the AO-Ti was more conducive to maintain the skeletal morphology of MSCs. The results of osteogenic related proteins expression showed that the amount of BMP-2 on AO-Ti group was the highest in the inflammatory conditions, and followed the order of AO-Ti >HA coating-Ti >SLA-Ti >PT-Ti. What's more, the AO-Ti samples were more beneficial to promote the expression of osteogenic genes ALP, OCN, COL-I and Runx2 in the inflammatory conditions. The results of osteogenic properties in vivo showed that the gingival depth of the AO-Ti group was smaller than that on the other groups. Some new bone could be observed around the AO-Ti implant at two weeks. The bone binding rates on AO-Ti group was the highest of 81.3% after implanted for one year. The AO-Ti was beneficial to osteogenic differentiation than other modified titanium metals in inflammatory condition. The anodic oxidation is an effective surface modification method on titanium to promote bone regeneration.

Relationship of the Morphology and Size of Sella Turcica with Dental Anomalies and Skeletal Malocclusions.

This study aimed to assess the relationship of the morphology and size of the sella turcica (ST) with dental anomalies and skeletal malocclusions. This cross-sectional study was conducted on records of fixed orthodontic patients treated between 2013 and 2022. Cephalometric analysis was performed to determine the anteroposterior and vertical skeletal patterns. Preoperative panoramic radiographs and lateral cephalograms, intraoral photographs, and primary dental casts of patients were used to detect dental anomalies. Gender, sagittal and vertical skeletal patterns, dental anomalies, and dimensions (length, depth, and diameter), and morphology of the ST were all recorded according to the lateral cephalograms of patients. Data were analyzed using independent t-test, one-way and two-way ANOVA, Chi-square test, and log rank test (alpha = 0.05). The depth and diameter of the ST had no significant correlation with gender (p > 0.05); however, the length of the ST was significantly longer in males than females (p < 0.05). The morphology of the ST had a significant correlation with gender (p < 0.05). The ST morphology had a significant correlation with the anteroposterior skeletal pattern, microdontia, and tooth impaction as well (p < 0.05). The present results revealed a significant correlation of the ST morphology with the anteroposterior skeletal pattern, microdontia, and tooth impaction.

Radiation induces long-term muscle fibrosis and promotes a fibrotic phenotype in fibro-adipogenic progenitors.

Radiation-induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation-induced muscle pathology has not previously been explored. Four-week-old Male CBA or C57Bl/6J mice received a single dose (16Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56days post-IR (long-term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed. Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (P<0.05) and reduced the proportion of type I myofibres (P<0.05). Skeletal muscle fibrosis (P<0.05) was evident at 56days post-IR. The IR-limb had fewer endothelial cells (P<0.05) and fibro-adipogenic progenitors (FAPs) (P<0.05) at 56days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56days in the IR-limb (P<0.05). IR induced FAP senescence (P<0.05), increased their fibrogenic differentiation (P<0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (P<0.05) and fusion (P<0.05). Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.

Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.

Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using physical working capacity (power output) at a heart rate of 150 beats/min (PWC150) as an indicator of submaximal exercise capacity in subjects of the HERITAGE Family Study, we have undertaken multi-omics and in silico explorations of the underlying biology of PWC150 and its response to 20 wk of endurance training. Our goal was to illuminate the biological processes and identify panels of genes associated with human variability in intrinsic PWC150 (iPWC150) and its trainability (dPWC150). Our bioinformatics approach was based on a combination of genome-wide association, skeletal muscle gene expression, and plasma proteomics and metabolomics experiments. Genes, proteins, and metabolites showing significant associations with iPWC150 or dPWC150 were further queried for the enrichment of biological pathways. We compared genotype-phenotype associations of emerging candidate genes with reported functional consequences of gene knockouts in mouse models. We investigated the associations between DNA variants and multiple muscle and cardiovascular phenotypes measured in HERITAGE subjects. Two panels of prioritized genes of biological relevance to iPWC150 (13 genes) and dPWC150 (6 genes) were identified, supporting the hypothesis that genes and pathways associated with iPWC150 are different from those underlying dPWC150. Finally, the functions of these genes and pathways suggested that human variation in submaximal exercise capacity is mainly driven by skeletal muscle morphology and metabolism and red blood cell oxygen-carrying capacity.NEW & NOTEWORTHY Multi-omics and in silico explorations of the genes and underlying biology of submaximal exercise capacity and its response to 20 wk of endurance training were undertaken. Prioritized genes were identified: 13 genes for variation in submaximal exercise capacity in the sedentary state and 5 genes for the response level to endurance training, with no overlap between them. Genes and pathways associated with submaximal exercise capacity in the sedentary state are different from those underlying trainability.

Measuring skeletal muscle morphology in children with cerebral palsy – A scoping review update of the last 4 years

Measuring skeletal muscle morphology in children with cerebral palsy – A scoping review update of the last 4 years

Differences in Kinematic Changes From Self-Selected to Fast Speed Gait in Asymptomatic Adults With Radiological Signs of Femoro-Acetabular Impingement.

Femoro-acetabular impingement (FAI) may present as alterations in the skeletal morphology of the hip. Repercussions of FAI can be witnessed in self-selected speed walking as well as physical exercise such as running or fast speed walking. The aim of this study was to investigate changes in kinematics at different gait speeds in subjects presenting with radiological findings invoking FAI. One hundred thirty asymptomatic adults underwent biplanar X-rays with a calculation of 3D hip parameters: acetabular anteversion, abduction and tilt, vertical center edge angle (VCE), femoral anteversion, neck-shaft angle, acetabular coverage of the femoral head, femoral head diameter and neck length. Parameters were classified according to FAI clinical thresholds. Two groups were created: Control group (63 subjects having up to one subnormal hip parameter in favour of FAI) and Radiographic FAI group (67 subjects having ≥2 subnormal hip parameters that might cause FAI). All subjects underwent 3D gait analysis at self-selected and fast speed, from which kinematic parameters were generated. Arithmetic differences between fast and self-selected speed gait were considered as gait changes. Subjects in the Radiographic FAI group had decreased acetabular tilt (24 vs. 19˚), anteversion (19 vs. 16˚), abduction (55 vs. 53˚), femoral anteversion (18 vs. 14˚) and increased VCE (29 vs. 33˚, all p<0.05), compared to controls.Changes from self-selected to fast speed showed that subjects in the Radiographic FAI group had lower range of motion (ROM) pelvic rotation (7 vs. 4˚) and ROM hip flexion/extension (10 vs. 7˚), reduced hip extension (-4 vs. -2˚) and step length (16 vs. 13 cm; all p<0.05). The Radiographic FAI group had decreased acetabular abduction, anteversion and femoral anteversion in favour of FAI. When adapting from self-selected to fast speed gait, the Radiographic FAI group seemed to limit pelvic rotation and hip flexion/extension resulting in a decrease in step length. These kinematic limitations were previously reported in subjects with symptomatic FAI. Gait analysis could be considered as a functional diagnostic tool to assess FAI along with radiological assessment.

Effect of undercooling on clinopyroxene crystallization in a high K basalt: Implications for magma dynamics at Stromboli volcano

We present undercooling (∆T) experiments aimed at investigating the effect of growth kinetics on the textural and compositional evolution of clinopyroxene crystals growing from a high-K basalt erupted during the 2003 paroxysm of Stromboli volcano (Italy). The experiments were performed at P = 350 MPa, T = 1050–1210 °C, H2Omelt = 0–3 wt%, and fO2 = Ni-NiO + 1.5 buffer. An initial stage of supersaturation was imposed to the melt under nominally anhydrous (∆Tanh = 10–150 °C) and hydrous (∆Thyd = 25–125 °C) conditions. Afterwards, this supersaturation state was mitigated by melt relaxation phenomena over an annealing time of 24 h. Results show that plagioclase is the liquidus mineral phase of the high-K basalt at ∆Tanh = 10 °C and dominates the phase assemblage as the degree of undercooling increases. Conversely, clinopyroxene and spinel co-saturate the melt at ∆Thyd = 25 °C, followed by the subordinate formation of plagioclase. At ∆Tanh/hyd ≤ 50 °C, the textural maturation of clinopyroxene produces polyhedral crystals with {−111} (hourglass) and {hk0} (prism) sectors typical of a layer-by-layer growth mechanism governed by an interface-controlled crystallization regime. At ∆Tanh/hyd ≥ 75 °C, the attainment of dendritic and skeletal morphologies testifies to the establishment of diffusion-limited reactions at the crystal-melt interface. 3D reconstructions of synchrotron radiation X-ray microtomographic data reveal a composite growth history for clinopyroxene crystals obtained at ∆Tanh/hyd ≥ 95 °C. The early stage of melt supersaturation produces rosette-like structures composed of dendritic branches of clinopyroxene radiating from a common spinel grain, which acts as surface for heterogeneous nucleation. As diffusive relaxation phenomena progress over the annealing time, the elongate dendrites that constitute the inner crystal domain are partially infilled by the melt and develop skeletal overgrowths in the outer domain. With the increasing degree of undercooling, TAl and M1Ti cations are progressively incorporated in the lattice site of clinopyroxene at the expense of TSi and M1Mg cations. Because of the effect of H2Omelt on the liquidus depression and melt depolymerization, crystals obtained at ∆Thyd are also more enriched in TAl and M1Ti and depleted in TSi and M1Mg than those growing at ∆Tanh. The emerging picture is that the morphological and geochemical evolution of clinopyroxene is mutually controlled by the combined effects of melt supersaturation and relaxation phenomena. A new empirical relationship based on the cation exchange reactions in the lattice site of clinopyroxene is finally proposed to estimate the degree of undercooling governing the crystallization of augitic phenocrysts erupted during normal and violent explosions at Stromboli.

Different gait pattern in adolescence with patellofemoral instability

BackgroundPatellofemoral instability influences the gait pattern and activity level in adolescents. However, gait biomechanics to cope with recurrent patella instability and its relation to radiological findings has hardly been studied. MethodsWe retrospectively analyzed kinematic and kinetic gait analysis data, magnetic resonance images and X-ray of 32 adolescents with unilateral recurrent patellofemoral instability aged 12 to 18 years. Subjects were assigned to 3 groups based on their sagittal knee moment in the loading response and mid stance phase. Kinematic and kinetic differences among the groups were analyzed using a one-way ANOVA. A multinomial logistic regression model provided a further analysis of the relationship between gait biomechanics and MRI as well as X-ray parameters. FindingsAll three groups showed different characteristics of the knee kinematics during loading response and single stance: while the patella-norm-loading group showed a slightly reduced knee flexion (p 〈0,01), the patella-unloading group kept the knee nearly extended (p < 0,01) and patella-overloading group showed an increased knee flexion (p = 0,01) compared to the other groups. In single stance the patella-overloading group maintained increased knee flexion (p < 0,01) compared to patella-unloading group and patella-norm-loading group. None of the radiological parameters proved to be related to gait patterns. InterpretationThe paper describes different gait coping strategies and their clinical relevance in subjects with patellofemoral instability. However, we did not find any relation of gait biomechanics to skeletal morphology.

The response of coral skeletal nano structure and hardness to ocean acidification conditions.

Ocean acidification typically reduces coral calcification rates and can fundamentally alter skeletal morphology. We use atomic force microscopy (AFM) and microindentation to determine how seawater pCO2 affects skeletal structure and Vickers hardness in a Porites lutea coral. At 400 µatm, the skeletal fasciculi are composed of tightly packed bundles of acicular crystals composed of quadrilateral nanograins, approximately 80-300 nm in dimensions. We interpret high adhesion at the nanograin edges as an organic coating. At 750 µatm the crystals are less regular in width and orientation and composed of either smaller/more rounded nanograins than observed at 400 µatm or of larger areas with little variation in adhesion. Coral aragonite may form via ion-by-ion attachment to the existing skeleton or via conversion of amorphous calcium carbonate precursors. Changes in nanoparticle morphology could reflect variations in the sizes of nanoparticles produced by each crystallization pathway or in the contributions of each pathway to biomineralization. We observe no significant variation in Vickers hardness between skeletons cultured at different seawater pCO2. Either the nanograin size does not affect skeletal hardness or the effect is offset by other changes in the skeleton, e.g. increases in skeletal organic material as reported in previous studies.

Alterations in skeletal muscle morphology and mechanics in juvenile male Sprague Dawley rats exposed to a high-fat high-sucrose diet

Although once a health concern largely considered in adults, the obesity epidemic is now prevalent in pediatric populations. While detrimental effects on skeletal muscle function have been seen in adulthood, the effects of obesity on skeletal muscle function in childhood is not clearly understood. The purpose of this study was to determine if the consumption of a high-fat high-sucrose (HFS) diet, starting in the post-weaning period, leads to changes in skeletal muscle morphology and mechanics after 14 weeks on the HFS diet. Eighteen 3-week-old male CD-Sprague Dawley rats were randomly assigned to a HFS (C-HFS, n = 10) or standard chow diet (C-CHOW, n = 8). Outcome measures included: weekly energy intake, activity levels, oxygen consumption, body mass, body composition, metabolic profile, serum protein levels, and medial gastrocnemius gene expression, morphology, and mechanics. The main findings from this study were that C-HFS rats: (1) had a greater body mass and percent body fat than control rats; (2) showed early signs of metabolic syndrome; (3) demonstrated potential impairment in muscle remodeling; (4) produced lower relative muscle force; and (5) had a shift in the force–length relationship, indicating that the medial gastrocnemius had shorter muscle fiber lengths compared to those of C-CHOW rats. Based on the results of this study, we conclude that exposure to a HFS diet led to increased body mass, body fat percentage, and early signs of metabolic syndrome, resulting in functional deficits in MG of childhood rats.

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy.

DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects. DJ-1 expression decreased in atrophied muscles of aged human (young men, n=2; old with aged men, n=2; young women, n=2; old with aged women, n=2) and immobilization mice (n=6, P<0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n=8; MDKO, n=9). DJ-1-deficient muscles were slightly dystrophic (Flox, n=7; MDKO, n=8; P<0.05), with impaired physical activities and oxidative capacity (n=8, P<0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n=5, P<0.01) and more central nuclei than control mice (Flox, n=7; MDKO, n=6; P<0.05), without alteration in muscle fibre types (Flox, n=6; MDKO, n=7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo. Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.

Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3

AimsTo identify N-acetyltransferase 10 (NAT10) and its downstream signaling pathways in myocytes and skeletal muscle, and to investigate its role in inflammation-induced muscle atrophy. Materials and methodsCecal ligation and puncture models were used to induce sepsis in C57BL/6 mice, which were treated with either a NAT10 inhibitor or a control agent. The therapeutic effect of NAT10 inhibitor was investigated by evaluating the mass, morphology, and molecular characteristics of mouse skeletal muscle. C2C12 cells were stimulated with LPS, and the expression of the NAT10 gene, downstream protein content, and atrophy phenotype were analyzed using a NAT10 inhibitor, to further explore the atrophic effect of NAT10 on C2C12 differentiated myotubes. ResultsGene set enrichment analysis revealed that NAT10 expression was elevated in the Lateral femoris muscle of patients with ICUAW. In vitro and in vivo experiments showed that sepsis or LPS induced the upregulation of NAT10 expression in skeletal muscles and C2C12 myotubes. Skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with atrophic response in sepsis models. Remodelin ameliorated the LPS-induced skeletal muscle weight loss, as well as muscular atrophy, and improved survival. Remodelin reversed the atrophy program that was induced by inflammation through the downregulation of the ROS/NLRP3 pathway, along with the inhibition of the expression of MuRF1 and Atrogin-1. ConclusionNAT10 is closely related to skeletal muscle atrophy during sepsis. Remodelin improves the survival rate of mice by improving the systemic inflammatory response and skeletal muscle atrophy by downregulating the ROS/NLRP3 signaling pathway.

Intrageneric taxonomic distinction based on morphological variation in the macaque (Macaca) skeleton.

Taxonomic classification is important for understanding the natural world, yet current methods for species assessment often focus on craniodental morphology rather than the entire skeleton. Moreover, it is currently unknown how much variation could, or should, exist intragenerically. Here, we tested whether taxonomy can be accurately predicted based on patterns of morphological variation in macaques (H1 ) and whether postcranial bones reflect subgeneric macaque taxonomy similarly, or better, than the cranium (H2 ). Data included 3D scans of cranial and postcranial bones for eight macaque species (Macaca arctoides, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Macaca nemestrina, Macaca nigra, Macaca radiata, and Macaca sylvanus). Fixed anatomical and semilandmarks were applied to scans of eight skeletal elements (crania = 45; mandible = 31; scapula = 66; humerus = 38; radius = 33; os coxa = 28; femur = 40; tibia = 40). For each skeletal element, regression analyses were performed to minimize the effects of sexual dimorphism. Between-groups principal components analysis was used to visualize the major patterns of among-species morphological variation, while the strength of correct taxon classification was measured with discriminant function analysis. Results suggested accepting the alternate hypothesis that different macaque species can be distinguished morphologically. Both cranial and many postcranial elements appeared to possess a taxonomic signal, and the limb bones-especially the upper limb-are reported to be more useful for taxonomic assessment than previously realized. Theoretically, certain behaviors and/or ecogeographical factors, as well as phylogeny, influenced skeletal morphology in macaques, likely contributing to taxonomic distinctions among different species.

Skeletal anatomy of the pectoral fin in mudskipper species from terrestrial and aquatic habitats.

Mudskippers are a group of amphibious fishes in the family Oxudercidae, whose species inhabit a range of habitats from mostly aquatic to mostly terrestrial. Most of our understanding about habitat preference comes from natural history observations, particularly where they are collected (i.e., low intertidal vs. high intertidal regions). Mudskippers have undergone several morphological changes to accommodate a terrestrial life, including major changes to the pectoral and pelvic girdles. These changes result in a novel crutching gait, which mudskippers use to move over land. Though the appendicular morphology and crutching gait of mudskippers have been described in some species, few studies have compared skeletal structures across the family. In our study, we use microcomputed tomography (µCT) scans to compare the skeletal anatomy of 16 species of aquatic and terrestrial mudskippers. Linear discriminant analysis is used to analyze measurements obtained through geometric morphometrics (landmarks). We found bone structures of the pectoral region in the terrestrial group were significantly longer and wider than those in the aquatic group. Furthermore, a significant difference in anatomy is shown between terrestrial and aquatic genera with both axial and appendicular elements contributing to the separation between groups. This work describes the differences in skeletal morphology associated with terrestriality in mudskippers and provides valuable insights into specific anatomical characteristics contributing to their adaptation to novel environments.

Deletion of Nmnat1 in Skeletal Muscle Leads to the Reduction of NAD+ Levels but Has No Impact on Skeletal Muscle Morphology and Fiber Types.

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that mediates many redox reactions in energy metabolism. NAD+ is also a substrate for ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerase and sirtuin, respectively. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) is a NAD+ biosynthesizing enzyme found in the nucleus. Recent research has shown that the maintaining NAD+ levels is critical for sustaining muscle functions both in physiological and pathological conditions. However, the role of Nmnat1 in skeletal muscle remains unexplored. In this study, we generated skeletal muscle-specific Nmnat1 knockout (M-Nmnat1 KO) mice and investigated its role in skeletal muscle. We found that NAD+ levels were significantly lower in the skeletal muscle of M-Nmnat1 KO mice than in control mice. M-Nmnat1 KO mice, in contrast, had similar body weight and normal muscle histology. Furthermore, the distribution of muscle fiber size and gene expressions of muscle fiber type gene expression were comparable in M-Nmnat1 KO and control mice. Finally, we investigated the role of Nmnat1 in muscle regeneration using cardiotoxin-induced muscle injury model, but muscle regeneration appeared almost normal in M-Nmnat1 KO mice. These findings imply that Nmnat1 has a redundancy in the pathophysiology of skeletal muscle.

Effect of an acute long-duration exercise bout on skeletal muscle lipid droplet morphology, GLUT 4 protein, and perilipin protein expression.

Smaller lipid droplet morphology and GLUT 4 protein expression have been associated with greater muscle oxidative capacity and glucose uptake, respectively. The main purpose of this study was to determine the effect of an acute long-duration exercise bout on skeletal muscle lipid droplet morphology, GLUT4, perilipin 3, and perilipin 5 expressions. Twenty healthy men (age 24.0 ± 1.0 years, BMI 23.6 ± 0.4 kg/m2) were recruited for the study. The participants were subjected to an acute bout of exercise on a cycle ergometer at 50% VO2max until they reached a total energy expenditure of 650kcal. The study was conducted after an overnight fast. Vastus lateralis muscle biopsies were obtained before and immediately after exercise for immunohistochemical analysis to determine lipid, perilipin 3, perilipin 5, and GLUT4 protein contents while GLUT 4 mRNA was quantified using RT-qPCR. Lipid droplet size decreased whereas total intramyocellular lipid content tended to reduce (p=0.07) after an acute bout of endurance exercise. The density of smaller lipid droplets in the peripheral sarcoplasmic region significantly increased (0.584 ± 0.04 to 0.638 ± 0.08 AU; p=0.01) while larger lipid droplets significantly decreased (p<0.05). GLUT4 mRNA tended to increase (p=0.05). There were no significant changes in GLUT 4, perilipin 3, and perilipin 5 protein levels. The study demonstrates that exercise may impact metabolism by enhancing the quantity of smaller lipid droplets over larger lipid droplets.