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Background Chondroclasts and osteoclasts have been previously identified as the cells capable of resorbing mineralized cartilage and bone matrices, respectively. While both cell types appear morphologically similar, contain comparable ultrastructural features, and express tartrate-resistant acid phosphatase (TRAP), however, no information is available about the genomic similarities and differences between osteoclasts and chondroclasts. Methods To address this question, we laser captured homogeneous populations of TRAP-positive cells that interact with bone (osteoclasts) and TRAP-positive cells that interact with mineralized cartilage (chondroclasts) on the same plane from murine femoral fracture callus sections. We then performed a global transcriptome profiling of chondroclasts and osteoclasts by utilizing a mouse genome Agilent GE 4X44K V2 microarray platform. Multiple computational approaches and interaction networks were used to analyze the transcriptomic landscape of osteoclasts and chondroclasts. Results Our systematic and comprehensive analyses using hierarchical clustering and principal component analysis (PCA) demonstrate that chondroclasts and osteoclasts are transcriptionally distinct cell populations and exhibit discrete transcriptomic signatures as revealed by multivariate analysis involving scatter plot, volcano plot, and heatmap analysis. TaqMan qPCR was used to validate the microarray results. Intriguingly, the functional enrichment and integrated network analyses revealed distinct Gene Ontology terms and molecular pathways specific to chondroclasts and osteoclasts and further suggest that subsets of metabolic genes were specific to chondroclasts. Protein-protein interaction (PPI) network analysis showed an abundance of structured networks of metabolic pathways, ATP synthesis, and proteasome pathways in chondroclasts. The regulatory network analysis using transcription factor-target gene network predicted a pool of genes including ETV6, SIRT1, and ATF1 as chondroclast-specific gene signature. Conclusions Our study provides an important genetic resource for further exploration of chondroclast function in vivo. To our knowledge, this is the first demonstration of genetic landscape of osteoclasts from chondroclasts identifying unique molecular signatures, functional clustering, and interaction network.

We propose a new concept for measuring the affinity between fields of academic research. The importance of interdisciplinary research has been increasingly emphasized in recent years. The degree of interdisciplinarity of a research article can be determined using bibliographic information from the cited literature. However, the properties of the affinity of each field to other fields have not yet been discussed. Therefore, we employ our method to quantify the affinity between 27 research fields using academic journal data from the citation and abstract database Scopus. We show that the affinity between fields should be viewed from two perspectives: the affinity of other fields to the field of interest, and the affinity of the field of interest to other fields. We identify the fields of “Arts and Humanities” and “Social Sciences”, and “Earth and Planetary Sciences” and “Environmental Sciences”, as those with the highest bidirectional affinity. We also demonstrate that affinity to “Medicine” is particularly high, with seven fields of interest having the highest affinity to this field: “Biochemistry, Genetics and Molecular Biology”, “Immunology and Microbiology”, “Neuroscience”, “Pharmacology, Toxicology and Pharmaceutics”, “Nursing”, “Dentistry”, and “Health Professions”.

Tryptase is a serine protease that is released from mast cells during allergic responses. Tryptase inhibitors are being explored as treatments for allergic inflammation in the skin and respiratory system, most notably asthma. Here we report direct tryptase inhibition by natural product compounds. Candidate inhibitors were identified by computational screening of a large (98,000 compounds) virtual library of natural product compounds for tryptase enzymatic site binding. Biochemical assays were used to validate the predicted anti-tryptase activity in vitro, revealing a high (four out of six) success rate for predicting binding using the computational docking model. We further assess tryptase inhibition by a biflavonoid scaffold, whose structure-activity relationship is partially defined by assessing the potency of structurally similar analogs.

The October effect is known as a rapid and strong decrease in the signal amplitude of radio waves with very low frequency (VLF), reflected at the lowest edge of the ionosphere. This strong decrease can be observed only during the daytime. Although the October effect is long known, it is hardly investigated and its mechanism is still unknown. To get closer to a mechanism, we answer why the October effect does not occur during nighttime. Therefore, average characteristics of the October effect are obtained from different VLF transmitter‐receiver combinations. The occurrence of the October effect is then compared with characteristics of the neutral atmosphere temperature at VLF reflection heights as it seems to act as a proxy for the unknown mechanism. The temperature shows an asymmetric seasonal behavior at daytime VLF reflection heights poleward of 50°N but not during the nighttime, resulting in the October effect. Plain Language Summary The October effect is known as a rapid and strong decrease in the signal amplitude of radio waves with very low frequency, reflected at the lowest edge of the ionosphere (60–90 km). This strong decrease can be observed only during the daytime. Although the October effect has been long known, it is hardly investigated and its mechanism is still unknown. To get one step closer to a mechanism, we want to answer the question of why the October effect does not occur during nighttime. There are two main reasons why the October effect does not occur during nighttime. First, the radio wave reflection height is at around 70 km during daytime and at 85 km during nighttime. The second is the different behavior of the temperature at these two altitudes. While the temperature follows the seasonal cycle of the sun at 85 km, it shows an asymmetric behavior between spring and autumn at 70 km. This unexpected behavior of the temperature at 70 km leads to the October effect during the daytime only. Key Points Strong and rapid decrease in VLF amplitude in October Spring‐fall asymmetry in VLF amplitude and lower mesospheric temperature Asymmetry only at daytime VLF reflection height

PIM3 (Proviral Integration site for Maloney murine leukemia virus kinase 3) is a proto-oncogene with serine/threonine kinase activity that prevents apoptosis, promotes cell survival, and stimulates protein translation. In addition, PIM3 functions in inflammation and immunity pathways. PIM3 inhibitors are being developed to treat cancer and inflammation-related disorders. Here we screen a 98,000 compound virtual library of natural products to identify those that are predicted to fit in the ATP site of PIM3. Since the structure of PIM3 has not been determined experimentally, we performed molecular structure prediction using the SWISS-MODEL tool to generate a PIM3 model structure for in silico screening. Compounds predicted to fit the ATP binding site of PIM3 were validated using biochemical assays, revealing activity against PIM3 for all eight candidates, with potencies mostly in the micromolar range. We tested several analogs of two validated candidates, the diosgenin glycoside dioscin and the biflavonoid hinokiflavone. Among five dioscin analogs, three exhibit similar potency against PIM3, and with some selectivity for PIM3 versus PIM1 and 2. Meanwhile, three of seven biflavonoid analogs exhibit sub-micromolar IC50 potency against PIM3, but with less selectivity for PIM3 versus PIM1 and 2.

Data from a long time series of temperature, salinity, and nutrient measurements in Disko Bay (West Greenland) reveal a marked change in the water characteristics during recent years. Seasonal dynamics in the upper 150 m of the water column were highly affected by the seasonality in meteorological conditions, while the deeper water strata were more stable and were primarily influenced by large-scale circulation patterns. There was a marked increase in the average water temperatures at 200-m depth in spring 1997, with the long-term average increasing from 1.30°C to 2.25°C. Weekly data from 1996 to 1997 show that the sudden change in bottom water occurred in April 1997, due to the inflow of a larger proportion of North Atlantic water, which propagated north along the coast before entering the bay. Further support for this inflow was found when tracing the relative proportion of Atlantic water in the bay, using inorganic nutrients. These changes in the oceanography of the bay will not only lead to further glacial retreat but will also affect the local marine ecosystem by changing the relative dominance of major copepod species that overwinter in bottom waters of the bay.

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.

Urban and peri-urban agriculture (UPA) in West African countries is developing rapidly in response to population growth and changing consumer preferences. Furthermore, UPA offers opportunities to secure income and social integration for the urban poor. However, little is known about household (HH) income security effects of the ongoing shift in UPA land use from crops that do not rely on insect pollinators for fruit development (e.g., sorghum and millet) to pollinator-dependent crops. In our study we developed a Household Vulnerability Index (HVI) for 224 HHs along a rural–urban gradient of Ouagadougou, Burkina Faso. The HVI indicates to which degree total HH revenue could be affected by a decline in insect pollinators. HH specific relative reduction of agricultural revenue ranged from 0 to −0.83, a reduction in HHs’ revenue of up to 83%, depending on the crops’ level of pollinator dependency. Half of the studied HHs (n = 108) showed an HVI of 0 and remained unaffected by a decline in pollinators. Nevertheless, mean HVI was highest for urban HHs; making these HHs most vulnerable for loss of pollination services. As in urban areas changes in insect-mediated pollination services are expected, the development of resilient UPA systems must consider “pollinator-friendly” landscape management.

Context:Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage.Objective: This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV).Materials and methods: Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV. Both compounds were then tested in virus spread inhibition and virus yield reduction (VYR) assays of VACV. KPB-100 was further tested in viral cytopathic effect (CPE) inhibition assay of HHV-2 TK-mutant and VYR assay of HHV-1 WT.Results: KPB-100 and KPB-200 inhibited HHV-2 at IC50 values of 2.5 and 2.9 μg/mL, respectively, and VACV at IC50 values of 3.1 and 7.4 μg/mL, respectively, in plaque reduction assays. In virus spread inhibition assay of VACV KPB-100 and KPB-200 yielded IC50 values of 1.63 and 13.2 μg/mL, respectively, and KPB-100 showed a nearly 2-log reduction in virus in VYR assay of VACV at 20 μg/mL. Finally, KPB-100 inhibited HHV-2 TK- at an IC50 value of 4.5 μg/mL in CPE inhibition assay and HHV-1 at an IC90 of 3.0 μg/mL in VYR assay.Discussion and conclusion: Both compounds are promising targets for synthetic optimization and in vivo study. KPB-100 in particular showed strong inhibition of all viruses tested.

Cell-cell and cell-substrate adhesions are sites of dramatic actin rearrangements and where actin-membrane connections are tightly regulated. Zyxin-VASP complexes localize to sites of cell-cell and cell-substrate adhesion and function to regulate actin dynamics and actin-membrane connections at these sites. To accomplish these functions, zyxin recruits VASP to cellular sites via proline-rich binding sites near zyxin’s amino terminus. While the prevailing thought has been that zyxin simply acts as a scaffold protein for VASP binding, the identification of a LIM domain-VASP interaction could complicate this view. Here we assess how zyxin-VASP binding through both the proline rich motifs and the LIM domains alters specific VASP functions. We find that neither individual interaction alters VASP’s actin regulatory activities. In contrast, however, we find that full-length zyxin dramatically reduces VASPmediated actin bundling and actin assembly. Taken together, these results suggest a model where zyxin-VASP complexes occur in complex organizations with suppressed actin regulatory activity.