Human osteoblasts obtained from distinct periarticular sites demonstrate differences in biological function in vitro.

AIMS: Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components. METHODS: Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization. RESULTS: Osteoblasts from the acetabulum showed lower proliferation (p = 0.034), cumulative collagen release (p < 0.001), and ALP expression (p = 0.009), and produced less mineral (p = 0.006) than those from the femoral neck. Osteoblasts from the tibia produced significantly less collagen (p = 0.021) and showed lower ALP expression than those from the distal femur. CONCLUSION: We have demonstrated for the first time an anatomical regional variation in the biological behaviours of osteoblasts on either side of the hip and knee joint. The lower osteoblast proliferation, matrix production, and mineralization from the acetabulum compared to those from the proximal femur may be reflected in differences in bone formation and implant fixation at these sites. Cite this article: Bone Joint Res 2021;10(9):611-618

Faint dwarfs as a test of DM models: WDM vs. CDM

We use high resolution Hydro$+$N-Body cosmological simulations to compare the assembly and evolution of a small field dwarf (stellar mass ~ 10$^{6-7}$ M$\odot$, total mass 10$^{10}$ M$\odot$ in $\Lambda$ dominated CDM and 2keV WDM cosmologies. We find that star formation (SF) in the WDM model is reduced and delayed by 1-2 Gyr relative to the CDM model, independently of the details of SF and feedback. Independent of the DM model, but proportionally to the SF efficiency, gas outflows lower the central mass density through `dynamical heating', such that all realizations have circular velocities $<$ 20kms at 500$~$pc, in agreement with local kinematic constraints. As a result of dynamical heating, older stars are less centrally concentrated than younger stars, similar to stellar population gradients observed in nearby dwarf galaxies. Introducing an important diagnostic of SF and feedback models, we translate our simulations into artificial color-magnitude diagrams and star formation histories in order to directly compare to available observations. The simulated galaxies formed most of their stars in many $\sim$10 Myr long bursts. The CDM galaxy has a global SFH, HI abundance and Fe/H and alpha-elements distribution well matched to current observations of dwarf galaxies. These results highlight the importance of directly including `baryon physics' in simulations when 1) comparing predictions of galaxy formation models with the kinematics and number density of local dwarf galaxies and 2) differentiating between CDM and non-standard models with different DM or power spectra.Comment: 13 pages including Appendix on Color Magnitude Diagrams. Accepted by MNRAS. Added one plot and details on ChaNGa implementation. Reduced number of citations after editorial reques

Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions

MOCVD of Cd(1-x)Zn(x)S/CdTe PV cells using an ultra-thin absorber layer

Ultra-thin Cd(₁ ₋ ₓ)Zn(ₓ)S/CdTe devices were produced by atmospheric pressure metal organic chemical vapour deposition (AP-MOCVD) with varying CdTe absorber thicknesses ranging from 1.0 to 0.2 mm and compared to baseline cells with total CdTe thickness of 2.25μ. The ultra-thin CdTe layers (≤1 μm) were intentionally doped with As to induce p-type conductivity in the absorber. Cell performance reduced with CdTe thickness, with the magnitude of photo-current generation loss becoming more significant for the very thin CdTe layers. The decline in cell performance was lower than the optically limited performance relating to a decrease in shunt resistance, Rsh, especially for the thinnest cells due to areas of incomplete CdTe coverage and large presence of pin-holes leading to micro-shorts. Incorporation of Zn into the CdS window layer improved cell performance for all devices except when 0.2 μm thick CdTe was used. This improvement was markedly in the blue region owing to enhanced optical transparency of the window layer. External quantum efficiency (EQE) measurements showed a red-shift of the window layer absorption edge due to leaching out of Zn during the CdCl₂ treatment. Reduction of the CdCl₂ deposition time was demonstrated to recover the blue response of the ultra-thin cells

The influence of barefoot and barefoot inspired footwear on the kinetics and kinematics of running in comparison to conventional running shoes.

Barefoot running has experienced a resurgence in footwear biomechanics literature, based on the supposition that it serves to reduce the occurrence of overuse injuries in comparison to conventional shoe models. This consensus has lead footwear manufacturers to develop shoes which aim to mimic the mechanics of barefoot locomotion. This study compared the impact kinetics and 3-D joint angular kinematics observed whilst running: barefoot, in conventional cushioned running shoes and in shoes designed to integrate the perceived benefits of barefoot locomotion. The aim of the current investigation was therefore to determine whether differences in impact kinetics exist between the footwear conditions and whether shoes which aim to simulate barefoot movement patterns can closely mimic the 3-D kinematics of barefoot running. Twelve participants ran at 4.0 m.s-1±5% in each footwear condition. Angular joint kinematics from the hip, knee and ankle in the sagittal, coronal and transverse planes were measured using an eight camera motion analysis system. In addition simultaneous tibial acceleration and ground reaction forces were obtained. Impact parameters and joint kinematics were subsequently compared using repeated measures ANOVAs. The kinematic analysis indicates that in comparison to the conventional and barefoot inspired shoes that running barefoot was associated significantly greater plantar-flexion at footstrike and range of motion to peak dorsiflexion. Furthermore, the kinetic analysis revealed that compared to the conventional footwear impact parameters were significantly greater in the barefoot condition. Therefore this study suggests that barefoot running is associated with impact kinetics linked to an increased risk of overuse injury, when compared to conventional shod running. Furthermore, the mechanics of the shoes which aim to simulate barefoot movement patterns do not appear to closely mimic the kinematics of barefoot locomotion

Genetic Signatures for \u3cem\u3eHelicobacter pylori\u3c/em\u3e Strains of West African Origin

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of H. pylori strains from seven globally distributed populations or subpopulations and identified encoded proteins that exhibited the highest levels of sequence divergence. These included secreted proteins, an LPS glycosyltransferase, fucosyltransferases, proteins involved in molybdopterin biosynthesis, and Clp protease adaptor (ClpS). Among proteins encoded by the cag pathogenicity island, CagA and CagQ exhibited the highest levels of sequence diversity. We then identified proteins in strains of Western African origin (classified as hspWAfrica by MLST analysis) with sequences that were highly divergent compared to those in other populations of strains. These included ATP-dependent Clp protease, ClpS, and proteins of unknown function. Three of the divergent proteins sequences identified in West African strains were characterized by distinct insertions or deletions up to 8 amino acids in length. These polymorphisms in rapidly evolving proteins represent robust genetic signatures for H. pylori strains of West African origin

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies