Bone Deposition Research Articles

Adherence of Escherichia coli and blood elements in titanium discs submitted to anodic oxidation. In vitro study

Modifications of implants by means of surface treatments are performed to optimize the biochemical interactions of the bone deposition process. However, if on the one hand they favor the adhesion of blood elements, on the other hand they can also enable the formation of biofilm. This study evaluated the adherence of blood cells and Escherichia coli in titanium discs submitted to surface treatments by anodic oxidation (OA), sandblasting followed by acid etching (JAT) compared with untreated discs (Li). To evaluate the adherence of microorganisms were performed: atomic force microscopy; Field Emission Gun Scanning Electron Microscopy (FEG-SEM); biofilm formation was evaluated by spectrophotometer turbidity analysis and colony forming unit (CFU/mL) before and after simulated brushing. For blood cell adherence, the blood collected from a patient was deposited and fixed on the discs and analyzed in the FEG-SEM being classified according to the "Blood Element Adherence Index". The results showed a slight increase in the adhesion of microorganisms in samples treated by anodic oxidation. However, the microorganisms were distributed singly and not in conglomerates, with no biofilm formation unlike the Li group. Regarding the adherence of blood elements, the Li group showed higher adherence and lower amount was found in the JAT group, but there was no statistically significant difference between the groups. The results of this study suggest that anodic oxidation treatment may favor the adherence of blood cells and fibrin mesh, contributing to the early stages of bone deposition.

Targeted radiocarbon dating of animal bones from ritual wetland depositions in early Iron Age (Denmark)

The biography and chronology of ritual wetland deposits of animal bones has proven difficult to establish and has been based on the study and typology of associated groups of objects (ceramics and weapons) deposited at the same site. As a result, animal bone deposits are often generalised and perceived in plural, even though several sites exhibit evidence of multiple, clearly separate deposits of individual animals or animal parts. To surmount these shortcomings, this study presents and discusses the results of targeted radiocarbon dating of animal bone depositions from a number of well-established ritual wetland sites dated to the early Iron Age within the area of present-day Denmark. The study includes 154 radiocarbon dates from 10 different sites. The results confirm that the biography of ritual animal bone depositions in wetland sites is highly complex and indicate that the use of wetlands during the early Iron Age for ritualized deposition of animal bones lasted for up to 800 years from the 4th – 5th century BC. The study also shows that domestic animal species were preferred over wild animals, and it confirms that some species may have held a special significance. It is further suggested that some animal species were deposited in wetland ritual depositions for a longer period of time than others, and that some wetland sites were in use through multiple centuries, whereas others were not. All in all, the study suggests a complex and dynamic use of wetlands and animals as part of early Iron Age ritual life.

Vitamin D and Systems Biology.

The biological actions of the vitamin D receptor (VDR) have been investigated intensively for over 100 years and has led to the identification of significant insights into the repertoire of its biological actions. These were initially established to be centered on the regulation of calcium transport in the colon and deposition in bone. Beyond these well-known calcemic roles, other roles have emerged in the regulation of cell differentiation processes and have an impact on metabolism. The purpose of the current review is to consider where applying systems biology (SB) approaches may begin to generate a more precise understanding of where the VDR is, and is not, biologically impactful. Two SB approaches have been developed and begun to reveal insight into VDR biological functions. In a top-down SB approach genome-wide scale data are statistically analyzed, and from which a role for the VDR emerges in terms of being a hub in a biological network. Such approaches have confirmed significant roles, for example, in myeloid differentiation and the control of inflammation and innate immunity. In a bottom-up SB approach, current biological understanding is built into a kinetic model which is then applied to existing biological data to explain the function and identify unknown behavior. To date, this has not been applied to the VDR, but has to the related ERα and identified previously unknown mechanisms of control. One arena where applying top-down and bottom-up SB approaches may be informative is in the setting of prostate cancer health disparities.

Solving a ‘puzzle’. The global 4.2 ka Bond Event at El Mirador cave (Sierra de Atapuerca, Burgos, Spain) and the importance of small mammal taphonomy to the interpretation of past environments and their climatic controls

The regional climatic context in which Chalcolithic (MIR5) and Bronze Age (MIR4) levels from El Mirador cave (Sierra de Atapuerca, Burgos, Spain) are framed is affected by the 4.2 ka cal. BP event, a global event defined as a cooling and aridification phase. Previous works based on palaeoenvironmental inferences indicate conflicting results regarding the possible impact of the event on vegetation and small mammals from MIR5. Pollen record illustrates a possible aridification episode that could match with the 4.2 ka cal. BP event, while the signal of this event is not clearly recorded in the small mammal assemblage, which indicates more humid environmental conditions than pollen record. Taphonomic analyses confirmed that the small mammal assemblages from MIR4 and MIR5 are the result of predation, supporting the involvement of European eagle owls ( Bubo bubo) in its formation. This avian raptor shows a marked preference for hunting animals living in the more open and wetter parts of their hunting range. Likewise, spontaneous specialisation on abundant prey species could also be observed under certain environmental conditions. This characteristic behaviour of eagle owls may have provided the contradictory results observed between the small mammal assemblage and palynological evidence. Nonetheless, taphonomic analyses also provided information about climatic conditions and fluctuations along time. The low incidence of manganese coatings and carbonate crusts deposits in small mammal bone remains from MIR5 support the presence of arid conditions during the formation of this level, which agreed with the aridification phase probably related to the 4.2 ka Bond Event inferred by palynological data from MIR5. These results provided a more robust conclusion about the paleoenvironmental contexts during the formation of Chalcolithic and Bronze Age levels at El Mirador cave.

Three Tesla magnetic resonance imaging detects oxalate osteopathy in patients with primary hyperoxaluria type I.

With declining kidney function and therefore increasing plasma oxalate, patients with primary hyperoxaluria type I (PHI) are at risk to systemically deposit calcium-oxalate crystals. This systemic oxalosis may occur even at early stages of chronic kidney failure (CKD) but is difficult to detect with non-invasive imaging procedures. We tested if magnetic resonance imaging (MRI) is sensitive to detect oxalate deposition in bone. A 3 Tesla MRI of the left knee/tibial metaphysis was performed in 46 patients with PHI and in 12 healthy controls. In addition to the investigator's interpretation, signal intensities (SI) within a region of interest (ROI, transverse images below the level of the physis in the proximal tibial metaphysis) were measured pixelwise, and statistical parameters of their distribution were calculated. In addition, 52 parameters of texture analysis were evaluated. Plasma oxalate and CKD status were correlated to MRI findings. MRI was then implemented in routine practice. Independent interpretation by investigators was consistent in most cases and clearly differentiated patients from controls. Statistically significant differences were seen between patients and controls (p < 0.05). No correlation/relation between the MRI parameters and CKD stages or Pox levels was found. However, MR imaging of oxalate osteopathy revealed changes attributed to clinical status which differed clearly to that in secondary hyperparathyroidism. MRI is able to visually detect (early) oxalate osteopathy in PHI. It can be used for its monitoring and is distinguished from renal osteodystrophy. In the future, machine learning algorithms may aid in the objective assessment of oxalate deposition in bone. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Micro-CT analysis of osteomyelitis of rabbit tibial for model establishment and biomaterials application in tissue engineering

Osteomyelitis is one of the most difficult diseases to treat in orthopedics field. The construction of animal models of osteomyelitis is now more mature but still lacks a deeper criterion other than “successful infection”. In this work, rabbit tibial osteomyelitis model with S. aureus infection was established. Whole tibia, cortical bone around bone window, and tibial condyle were characterized in considerable detail using micro-CT and other means at 2/4/6 weeks, respectively. The results show that in addition to the obvious inflammatory response and bone destruction, osteomyelitis caused some other effects on compact and cancellous bone, and in particular, changes in bone mineral density after infection were of interest. Although the modeling groups all exhibited osteolysis and bone loss, their overall bone mineral density averages and those of the control groups were mostly in the range of 870 mg/cm3 to 920 mg/cm3, without statistical difference. The results suggest that overall bone mineral density is determined by both bone destruction conditions and the amount of dead bone deposition. This work provides a reference basis for the selection of time points for the subsequent animal models establishment and some valuable reference indicators of the application of biomaterials in tissue engineering.

The effectiveness of polypeptides from phosvitin and eggshell membrane in enhancing the bioavailability of eggshell powder calcium and its accumulation in bones

The low-calcium-specific pathogen-free C57BL/6 (SPF–C57BL/6) mice were used to explore the effectiveness of phosvitin phosphopeptides (PPPs) and eggshell membrane peptides (EMPs) in improving the intestinal calcium absorption and promoting bone deposition of eggshell calcium (ESCa). Intake of ESCa + PPPs + EMPs significantly down regulated the abnormal elevation of serum alkaline phosphatase (ALP) induced by calcium deficiency. The CaCO3 group had lower calcium absorption rate (34.34%) and femur bone mineral density (BMD) (0.13 g/cm3), while the ESCa + PPPs + EMPs treatment significantly improved calcium absorption rate (55.01%) and femur BMD (0.15 g/cm3). The three-dimensional reconstruction images of mice femur showed that the ESCa + PPPs + EMPs group had a more complete, compact, and thicker trabecular structure than the low-calcium, CaCO3, and ESCa groups. These results indicated that the ESCa is a low-cost alternative calcium supplement to achieve adequate calcium intake, and the presence of polypeptides, such as PPPs and EMPs, is more beneficial to calcium absorption and deposition than the ESCa.

Non-coding RNAs in ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is a kind of disease that involves a variety of factors leading to ectopic bone deposition of the spinal ligament. Although the detailed mechanism is not clear, genetic factors play important roles in the development of this disease. Noncoding RNA (ncRNA) refers to an RNA molecule that is not translated into a protein but participates in the regulation of gene expression. Functionally important types of ncRNA associated with OPLL include long noncoding RNA, microRNA, and circular RNA. We listed the differentially expressed ncRNAs in OPLL patients and normal controls to find the ncRNAs most relevant to the pathogenesis of the disease. The potential regulatory networks of ncRNA in OPLL cells were analyzed based on their most abundant signal transduction pathway data. The analysis of the highly connected ncRNAs in the regulatory network suggests that they play an important role in OPLL. These findings provide new directions for the study of OPLL pathogenesis and therapeutic targets. In this paper, we reviewed and analyzed the literature on ncRNAs in OPLL published in recent years, aiming to help doctors better understand and treat this disease.

Manganese-methionine chelate improves antioxidant activity, immune system and egg manganese enrichment in the aged laying hens.

It has been reported that supplementation of manganese (Mn) could alleviate the negative effects of age on egg quality in laying hens. However, limited information is available on compensatory ways in order to reduce the adverse effects of hen age on health and Mn deposition in the body. The objectives were to investigate the effect of organic and inorganic sources of Mn on antioxidant activity, immune system, liver enzymes, shell quality and Mn deposition in the tissues of older laying hens. A total of 250, 80-week-old Leghorn laying hens (w36) were allocated into five treatment groups with five replications in a completely randomised design. Treatments were control (without Mn supplementation), 100% Mn sulphate, 75% Mn sulphate+25% organic Mn chelate, 50% Mn sulphate+50% organic Mn chelate and 25% Mn sulphate+75% organic Mn chelate. The groups fed 50 and 75% organic Mn chelate exhibited the lowest feed conversion ratio, as well as the maximum laying percentage, and egg weight and mass. Except to those fed 75% Mn sulphate, the hens received Mn supplements either as organic or inorganic, had higher immunoglobulin G and M compared with the control (p<0.05). A significant elevation in the values of superoxide dismutase was observed in the hens receiving 50 and 75% organic Mn chelate when compared with the other treatments. The ALP activity decreased with increasing organic Mn chelate. Mn supplementation, either as organic or inorganic, increased Mn deposition in bone, egg yolk and shell, serum and liver. Dietary supplementation with 50-75% Mn-methionine has the potential to replace Mn-sulphate in laying hens' diet for improving eggshell quality, Mn deposition in the eggshell, antioxidant capacity and immune response, as well as improving laying performance, egg weight and feed conversion ratio.

An uncommon “third window” in retrofenestral otosclerosis

Otosclerosis is an otologic disease characterized by disordered resorption and deposition of the otic capsule bone. It can lead to progressive conductive, mixed or sensorineural Hearing Loss (HL). In rare cases, it manifests itself with a tendency for massive bone resorption with subsequent formation of cavities (“cavitating otosclerosis”). Cavities can sometimes realize communication between the Cerebrospinal Fluid (CSF) at the Internal Auditory Canal (IAC) and the cochlear duct. In these uncommon cases, a “third-window” phenomenon may be established as a concomitant cause of conductive HL. Therefore, the feasibility of stapes surgery should be evaluated, without underestimating the risk of gusher complications. In this report, we discuss the case of a female patient affected by cavitating otosclerosis realizing a connection between IAC and cochlear duct, with mixed hearing loss.

Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells

BackgroundBone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSCs) have shown potential as cell-based therapies for cartilage and bone injuries and are used increasingly in human and veterinary practice to facilitate the treatment of orthopedic conditions. However, human and rodent studies have documented a sharp decline in chondrogenic and osteogenic differentiation potential with increasing donor age, which may be problematic for the important demographic of older orthopedic patients. The aim of this study was to identify the effect of donor age on the chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs in vitro.BM- and AT-MSCs and dermal fibroblasts (biological negative control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥ 22 years). Chondrogenic differentiation performance was assessed quantitatively by measuring pellet size, matrix proteoglycan levels, and gene expression of articular cartilage biomarkers. Osteogenic differentiation performance was assessed quantitatively by measuring alkaline phosphatase activity, calcium deposition, and gene expression of bone biomarkers.ResultsChondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs declined with increasing donor age. BM-MSCs had a higher chondrogenic differentiation performance. AT-MSCs showed minimal chondrogenic differentiation performance in all age groups. For osteogenesis, alkaline phosphatase activity was also higher in BM-MSCs, but BM-MSCs calcium deposition was affected by donor age earlier than AT-MSCs. Chondrogenic and osteogenic differentiation performance of BM-MSCs exhibited a decline as early as between the newborn and yearling samples. Steady state levels of mRNA encoding growth factors, chondrogenic, and osteogenic biomarkers were lower with increasing donor age in both MSC types.ConclusionsThe data showed that chondrogenic and osteogenic differentiation performance of equine BM-MSCs declined already in yearlings, and that AT-MSCs showed minimal chondrogenic potential, but were affected later by donor age with regards to osteogenesis (calcium deposition). The results highlight the importance of donor age considerations and MSC selection for cell-based treatment of orthopedic injuries and will help inform clinicians on when to implement or potentially cryopreserve cells. Moreover, the study provides molecular targets affected by donor age.

Pachyosteosclerosis, rhamphotheca and enhanced sensory capabilities of the premaxillae of Hyperodapedon (Archosauromorpha, Rhynchosauria): implications for foraging at the sediment–water interface

AbstractThe external morphology and microanatomy of 32 partial and complete Hyperodapedon premaxillae was examined to assess their functional attributes. This revealed morphological correlates for innervation of Hyperodapedon premaxillae in the form of posteriorly opening enlarged neurovascular foramina associated with several grooves, and a prominent neurovascular sulcus. Scanning electron microscopy shows numerous small, circular foramina in clusters along the lateroventral surface towards the anterior tip and along the ventral edge, often in a preferred orientation. These are found associated with high rugosity along the elongated anterolateral depression, and were related to nutrient supply and/or part of the neurovascular system. Selected premaxillae show extremely high bone compactness indices (especially at the anterior end) suggesting specialized osteosclerotic conditions, and dense and compact bone microstructure with almost no clear transition between the outer compact cortex and inner core. With ontogeny, the premaxillae became lateromedially thickened by deposition of lamellar zonal bone, and highly vascularized and dense from intense Haversian remodelling, suggesting pachyosteosclerosis of the premaxillae. Other characteristic features include profuse open vascular channels or a frayed margin at the anteroventral tip, and dense bundles of long and wavy extrinsic fibres. These features, along with high bone compactness, decrease posteriorly towards the naris. It is proposed that the Hyperodapedon premaxillae were covered by keratinized epithelium or rhamphotheca at the anterior end, and had heightened sensory capabilities that aided foraging for mussels and other invertebrates in soft sediments under shallow water. Such enhanced sensory capability is reported for the first time in an early‐diverging archosauromorph.

Estimating Prevalence of Oligometastases at Initial Staging of Neuroendocrine Tumors-Findings from a 68Ga DOTATATE PET (Ga68PET) Population-Based Registry

<h3>Purpose/Objective(s)</h3> Well differentiated neuroendocrine tumors (NET) have a long natural history. Determining the prevalence of oligometastases (OM) in NET would guide novel treatment and clinical trial designs. The Ontario PET-NET registry (OntPNR) is a population-based registry (since April 2019) of patients (pt) approved for Ga⁶⁸PET fulfilling the provincial access criteria. The objective is to describe the prevalence of OM disease at initial staging of well-differentiated NET. <h3>Materials/Methods</h3> A retrospective analysis of the OntPNR was conducted. DICOM images, reports and registry data were used. Staging cohort (SC) included pts with localized primary NETS and/or limited metastases (mets) where definitive surgery is planned. OM is defined as 1-5 metastatic lesions following Ga⁶⁸PET. <h3>Results</h3> Between May 2019 and Nov 2021, 1,084 pts underwent Ga⁶⁸PET. Of the 326 pts in the SC, M:F 1:1; grade 1 (159; 49%) & Ki67 low <6% (189; 58%) M1 (151; 46%). The most common primary sites were midgut (121; 37%) pancreatic (73; 22.4%) and unknown primaries (57; 17.5%). The primary tumors were previously removed prior to Ga⁶⁸PET staging scan in 49 (15%) patients. Metastases were present in 151/326 pts (46.3%). OM were identified in 30/326 (9.2%) pts [20 (13.2%) in the liver only and 10 (6.6%) extra-hepatic]. Median number of mets was 2 (Range 1-5). The most common mets site was liver (20; 67%), followed by bone (7; 23%) and peritoneal deposits (4: 13%). Pts in the OM cohort are more likely to be males (21/30; 70% OM vs 159/326; 49% SC); and had unknown primaries (8/30; 27% OM; 57/326; 17.5% SC). <h3>Conclusion</h3> OM occurred in 9.2% of NET pts with apparent localized primary NETs and or limited metastases where definitive surgery is planned, and staged with Ga68 DOTATATE PET CT. This estimate does not include pts who are OM that are induced (post treatment) or during follow up. Expansion of the definition of OM (e.g., up to 10 metastatic lesions) could further enhance our understanding of the pattern of NET spread. These population-based results can serve as the basis for epidemiological investigations and clinical trials planning.

Interpreting the mammal deposits of Cloggs Cave (SEAustralia),GunaiKurnaiAboriginal Country, through community‐led partnership research

AbstractPalaeontological animal bone deposits are rarely investigated through research partnerships where the local First Nations communities have a defining hand in both the research questions asked and the research processes. Here we report research undertaken through such a partnership approach at the iconic archaeological site of Cloggs Cave (GunaiKurnai Country, East Gippsland), in the southern foothills of SE Australia's Great Dividing Range.A new excavation was combined with detailed chronometric dating, high‐resolution 3D mapping and geomorphological studies. This allowed interpretation of a sequence of stratigraphic layers spanning from a lowermost excavated mixed layer dated to between 25,640 and 48,470 cal BP, to a dense set of uppermost, ash layers dated to between 1460 and 3360 cal BP. This long and well‐dated chronostratigraphic sequence enabled temporal trends in the abundant small mammal remains to be examined.The fossil assemblage consists of at least 31 taxa of mammals which change in proportions through time. Despite clear evidence that the Old Ancestors repeatedly carried vegetation into the cave to fuel cool fires (no visible vegetation grows in Cloggs Cave), we observed little to no evidence of cooking fires or calcined bone, suggesting that people had little involvement with the accumulation of the faunal remains. Small mammal bones were most likely deposited in the cave by large disc‐faced owls,Tyto novaehollandae(Masked Owl) orTyto tenebricosa(Sooty Owl).Despite being well dated and largely undisturbed, the Cloggs Cave assemblage does not appear to track known Late Quaternary environmental change. Instead, the complex geomorphology of the area fostered a vegetation mosaic that supported mammals with divergent habitat preferences. The faunal deposit suggests a local ancestral landscape characterised by a resilient mosaic of habitats that persisted over thousands of years, signalling that the Old Ancestors burned landscape fires to encourage and manage patches of different vegetation types and ages within and through periods of climate change.Read the freePlain Language Summaryfor this article on the Journal blog.

Cellularcommunication network factor 1 interlinks autophagy and ERK signaling to promote osteogenesis of periodontal ligament stem cells.

To investigate the effects of cellular communication network factor 1 (CCN1), a critical matricellular protein, on alveolar bone regeneration, and to elucidate the underlying molecular mechanism. In the process of orthodontic tooth movement, bone deposition on the tension side of human periodontal ligament stem cells (hPDLSCs) ensured high efficiency and long-term stability of the treatment. The matricellular protein CCN1 is responsive to mechanical stimulation, exhibiting important tasks in bone homoeostasis. However, the role and mechanism of CCN1 on alveolar bone remodeling of hPDLSCs remains unclear. The expression and distribution of CCN1 in rat periodontal ligament were detected by immunofluorescence staining and immunohistochemical staining. ELISA verified the secretion of CCN1 triggered by stretch loading. To examine the mineralization ability of hPDLSCs induced by CCN1, Western blotting, qRT-PCR, ARS, and ALP staining were performed. CCK-8 and cell migration assay were performed to detect the cell proliferation rate and the wound healing. PI3K/Akt, MAPK, and autophagy activation were examined via Western blotting and immunofluorescence. Mechanical stimuli induced the release of CCN1 into extracellular environment by hPDLSCs. Knockdown of CCN1 attenuated the osteogenesis of hPDLSCs while rhCCN1 enhanced the expression of Runx2, Col 1, ALPL, and promoted the mineralization nodule formation. CCN1 activated PI3K/Akt and ERK signaling, and blockage of PI3K/Akt signaling reversed the accelerated cell migration triggered by CCN1. The enhanced osteogenesis induced by CCN1 was abolished by ERK signaling inhibitor PD98059 or autophagy inhibitor 3-MA. Further investigation demonstrated PD98059 abrogated the activation of autophagy. This study demonstrated that CCN1 promotes osteogenesis in hPDLSCs via autophagy and MAPK/ERK pathway.

Use of Photobiomodulation Combined with Fibrin Sealant and Bone Substitute Improving the Bone Repair of Critical Defects.

In this preclinical protocol, an adjunct method is used in an attempt to overcome the limitations of conventional therapeutic approaches applied to bone repair of large bone defects filled with scaffolds. Thus, we evaluate the effects of photobiomodulation therapy (PBMT) on the bone repair process on defects filled with demineralized bovine bone (B) and fibrin sealant (T). The groups were BC (blood clot), BT (B + T), BCP (BC + PBMT), and BTP (B + T + PBMT). Microtomographically, BC and BCP presented a hypodense cavity with hyperdense regions adjacent to the border of the wound, with a slight increase at 42 days. BT and BTP presented discrete hyperdensing areas at the border and around the B particles. Quantitatively, BCP and BTP (16.96 ± 4.38; 17.37 ± 4.38) showed higher mean bone density volume in relation to BC and BT (14.42 ± 3.66; 13.44 ± 3.88). Histologically, BC and BCP presented deposition of immature bone at the periphery and at 42 days new bone tissue became lamellar with organized total collagen fibers. BT and BTP showed inflammatory infiltrate along the particles, but at 42 days, it was resolved, mainly in BTP. In the birefringence analysis, BT and BTP, the percentage of red birefringence increased (9.14% to 20.98% and 7.21% to 27.57%, respectively), but green birefringence was similar in relation to 14 days (3.3% to 3.5% and 3.5% to 4.2%, respectively). The number of osteocytes in the neoformed bone matrix proportionally reduced in all evaluated groups. Immunostaining of bone morphogenetic protein (BMP—2/4), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) were higher in BCP and BTP when compared to the BC and BT groups (p < 0.05). An increased number of TRAP positive cells (tartrate resistant acid phosphatase) was observed in BT and BTP. We conclude that PBMT positively influenced the repair of bone defects filled with B and T.

Chronic fracture and osteomyelitis in a large-bodied ornithomimosaur with implications for the identification of unusual endosteal bone in the fossil record.

Paleopathological diagnoses provide key information on the macroevolutionary origin of disease as well as behavioral and physiological inferences that are inaccessible via direct observation of extinct organisms. Here we describe the external gross morphology and internal architecture of a pathologic right second metatarsal (MMNS VP-6332) of a large-bodied ornithomimid (~432 kg) from the Santonian (Upper Cretaceous) Eutaw Formation in Mississippi, using a combination of X-ray computed microtomography (microCT) and petrographic histological analyses. X-ray microCT imaging and histopathologic features are consistent with multiple complete, oblique to comminuted, minimally displaced mid-diaphyseal cortical fractures that produce a "butterfly" fragment fracture pattern, and secondary osteomyelitis with a bone fistula formation. We interpret this as evidence of blunt force trauma to the foot that could have resulted from intra- or interspecific competition or predator-prey interaction, and probably impaired the function of the metatarsal as a weight-bearing element until the animal's death. Of particular interest is the apparent decoupling of endosteal and periosteal pathological bone deposition in MMNS VP-6332, which produces transverse sections exhibiting homogenously thick endosteal pathological bone in the absence of localized periosteal reactive bone. These distribution and depositional patterns are used as criteria for ruling out a pathological origin in favor of a reproductive one for unusual endosteal bone in fossil specimens. On the basis of MMNS VP-6332, we suggest caution in their use to substantiate a medullary bone identification in extinct archosaurians.

WHEN LUNG BECOMES BONE: A RARE CASE OF DENDRIFORM PULMONARY OSSIFICATION

WHEN LUNG BECOMES BONE: A RARE CASE OF DENDRIFORM PULMONARY OSSIFICATION

Immunomodulatory fibrous hyaluronic acid-Fmoc-diphenylalanine-based hydrogel induces bone regeneration.

To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm-diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro-computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect. A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.

El Niño frequency threshold controls coastal biotic communities.

El Niño has profound influences on ecosystem dynamics. However, we know little about how it shapes vertebrate faunal community composition over centennial time scales, and this limits our ability to forecast change under projections of future El Niño events. On the basis of correlations between geological records of past El Niño frequency and the species composition of bird and fish remains from a Baja California bone deposit that spans the past 12,000 years, we documented marked faunal restructuring when major El Niño events occurred more than five times per century. This tipping point has implications for the past and future ecology of eastern Pacific coastal environments.