Interactions among growth factors, cells, and extracellular matrix are critical to the regulation of directed cell migration and proliferation associated with development, wound healing, and pathologic processes. Here we report the association of PDGF-AB and -BB, but not PDGF-AA, with the extracellular glycoprotein SPARC. Complexes of SPARC and 125I-labeled PDGF-BB or -AB were specifically immunoprecipitated by anti-SPARC immunoglobulins. 125I-PDGF-BB and -AB also bound specifically to SPARC that was immobilized on microtiter wells or bound to nitrocellulose after transfer from SDS/polyacrylamide gels. The binding of PDGF-BB to SPARC was pH-dependent; significant binding was detectable only above pH 6.6. The interaction of SPARC with specific dimeric forms of PDGF affected the activity of this mitogen. SPARC inhibited the binding of PDGF-BB and PDGF-AB, but not PDGF-AA, to human dermal fibroblasts in a dose-dependent manner. The expression of SPARC and PDGF was minimal in most normal adult tissues but was increased after injury. Enhanced expression of both PDGF-B chain and SPARC was seen in advanced lesions of atherosclerosis. We suggest that the coordinate expression of SPARC and PDGF-B-containing dimers following vascular injury may regulate the activity of specific dimeric forms of PDGF in vivo.

SUMMARY: The Earth's mantle transition zone (MTZ) plays a key role in the thermal and compositional interactions between the upper and lower mantle. Seismic anisotropy provides useful information about mantle deformation and dynamics across the MTZ. However, seismic anisotropy in the MTZ is difficult to constrain from surface wave or shear wave splitting measurements. Here, we investigate the sensitivity to anisotropy of a body wave method, SS precursors, through 3-D synthetic modelling and apply it to real data. Our study shows that the SS precursors can distinguish the anisotropy originating from three depths: shallow upper mantle (80–220 km), deep upper mantle above 410 km, and MTZ (410–660 km). Synthetic resolution tests indicate that SS precursors can resolve $\ge $3 per cent azimuthal anisotropy where data have an average signal-to-noise ratio (SNR = 7) and sufficient azimuthal coverage. To investigate regional sensitivity, we apply the stacking and inversion methods to two densely sampled areas: the Japan subduction zone and a central Pacific region around the Hawaiian hotspot. We find evidence for significant VS anisotropy (15.3 ± 9.2 per cent) with a trench-perpendicular fast direction (93° ± 5°) in the MTZ near the Japan subduction zone. We attribute the azimuthal anisotropy to the grain-scale shape-preferred orientation of basaltic materials induced by the shear deformation within the subducting slab beneath NE China. In the central Pacific study region, there is a non-detection of MTZ anisotropy, although modelling suggests the data coverage should allow us to resolve at least 3 per cent anisotropy. Therefore, the Hawaiian mantle plume has not produced detectable azimuthal anisotropy in the MTZ.

We conducted a case-control study to determine whether a polymorphism in the CYP17 gene was associated with risk of breast cancer. We found an increased risk of advanced breast cancer in women carrying an A2 allele. The odds ratio was 2.5 [95% confidence interval (CI), 1.07-5.94] for regional or metastatic disease. Among controls, the A1/A1 genotype was associated with a later age at menarche. The reduced risk of breast cancer associated with a later age of menarche was largely limited to A1/A1 women: odds ratio, 0.47 (CI, 0.22-0.98) for breast cancer and later age at menarche among A1 homozygotes compared with 0.80 (CI, 0.51-1.27) for A1/A2 and A2/A2 genotypes. These findings suggest that the CYP17 genotype may be a biomarker for the onset of ovulation and advanced breast cancer risk.

Germanane, a hydrogen-terminated graphane analogue of germanium has generated interest as a potential 2D electronic material. However, the incorporation and retention of extrinsic dopant atoms in the lattice, to tune the electronic properties, remains a significant challenge. Here, we show that the group-13 element Ga and the group-15 element As, can be successfully doped into a precursor CaGe2 phase, and remain intact in the lattice after the topotactic deintercalation, using HCl, to form GeH. After deintercalation, a maximum of 1.1% As and 2.3% Ga can be substituted into the germanium lattice. Electronic transport properties of single flakes show that incorporation of dopants leads to a reduction of resistance of more than three orders of magnitude in H2O-containing atmosphere after As doping. After doping with Ga, the reduction is more than six orders of magnitude, but with significant hysteretic behavior, indicative of water-activation of dopants on the surface. Only Ga-doped germanane remains activated under vacuum, and also exhibits minimal hysteretic behavior while the sheet resistance is reduced by more than four orders of magnitude. These Ga- and As-doped germanane materials start to oxidize after one to four days in ambient atmosphere. Overall, this work demonstrates that extrinsic doping with Ga is a viable pathway towards accessing stable electronic behavior in graphane analogues of germanium.

The “U-phase,” a sodium-containing (alumino-ferrite-monosubstituent) AFm phase, has been observed to form in sodium-enriched highly alkaline cementitious systems, for example, of relevance to nuclear waste, and saline industrial brine management. But, minimal information is available of the U-phase's (e.g., solubility or thermodynamic properties) due to its limited stability and its tendency to transform into ettringite or monosulfoaluminate. Herein, the U-phase was systematically synthesized at four temperatures (5, 15, 25, and 50°C) and fully characterized in terms of its thermochemical properties. The average composition of the synthesized U-phase (4CaO·Al2O3·1.85SO3·0.85Na2O·12H2O) deviates slightly from typical disclosures in the literature. The solubility product of the U-phase formation was measured from conditions of oversaturation. The measured thermodynamic data accurately predicted experimental observations of U-phase formation in cementitious environments. In general, it was noted that the U-phase forms and persists (i.e., remains stable) at pH > 13.7 and [Na+] concentrations superior to 1 mol/L.

Abstract Background and Purpose Oligodendrocyte (OL) death is important in focal cerebral ischemia. TIMP-3 promotes apoptosis in ischemic neurons by inhibiting proteolysis of TNF-α superfamily of death receptors. Since OLs undergo apoptosis during ischemia, we hypothesized that TIMP-3 contributes to OL death. Methods Middle cerebral artery occlusion (MCAO) was induced in Timp-3 knockout (KO) and wild type (WT) mice with 24 or 72 h of reperfusion. Cell death in white matter was investigated by stereology and TUNEL. Mature or immature OLs were identified using antibodies against glutathione S-transferase-π (GST-π) and galactocerebroside (GalC), respectively. Expression and level of proteins were examined using immunohistochemistry and immunoblotting. Protein activities were determined using a FRET peptide. Results Loss of OL-like cells was detected at 72 h only in WT ischemic white matter where TUNEL showed greater cell death. TIMP-3 expression was increased in WT reactive astrocytes. GST-π was reduced in ischemic white matter of WT mice compared with WT shams with no difference between KO and WT at 72 h. GalC level was significantly increased in both KO and WT ischemic white matter at 72 h. However, the increase in GalC in KO mice was significantly higher than WT; most TUNEL-positive cells in ischemic white matter expressed GalC, suggesting TIMP-3 deficiency protects the immature OLs from apoptosis. There were significantly higher levels of cleaved caspase-3 at 72 h in WT white matter than in KO. Greater expression of MMP-3 and -9 was seen in reactive astrocytes and/or microglia/macrophages in WT at 72 h. We found more microglia/macrophages in WT than in KO, which were the predominant source of increased TNF-α detected in the ischemic white matter. TACE activity was significantly increased in ischemic WT white matter, which was expressed in active microglia/macrophages and OLs. Conclusions Our results suggested that focal ischemia leads to proliferation of immature OLs in white matter and that TIMP-3 contributes to a caspase-3-dependent immature OL death via TNF-α-mediated neuroinflammation. Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type.

Background

Failure of Alzheimer's disease and related diseases (ADRD) research studies to include and engage Black participants is a major issue, which limits the impact and generalizability of research findings. Little is known about participation of Black adults in online ADRD-related research registries.

Objectives

As part of the Community Engaged Digital Alzheimer's Research (CEDAR) Study, this study aims to increase our understanding of facilitators and barriers of Black adults to participating in ADRD-related online registries, as well as to understand their preferences for communication channels.

Design, setting, participants, measurements

We invited all Black participants enrolled in the Brain Health Registry (BHR) to complete a cross-sectional online survey. The survey consisted of rating scales and open-text questions asking about their attitudes towards brain health research, reasons for joining and continuing to participate in BHR, difficulties with participating, and preferences for modes of contact and website usage.

Results

Of all invited Black BHR participants (N=3,636), 198 (5.5%) completed the survey. The mean age was 58.4 (SD=11.3), mean years of education were 16.3 (SD=2.4), and 85.5% identified as female. Reported facilitators for joining and continuing to participate in BHR were personal interest (e.g., learning more about own brain health) and altruism (e.g., helping research). Among additional registry features which could encourage return, receiving feedback or scores about BHR tasks was rated the highest. Of those who found BHR participation difficult (21%), the most frequent reason was time burden. The most preferred way of receiving study information was via email. Participants reported that the websites that they used the most were YouTube and Facebook.

Discussion

The results of our study can inform the development of culturally-responsive registry features and engagement efforts to improve inclusion and participation of Black adults in online ADRD research. Providing participants with feedback about their registry performance and reducing the number of registry tasks are among the recommended strategies.