Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Extremely short duration interval exercise improves 24-h glycaemia in men with type 2 diabetes

PurposeReduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient exercise intervention that improves aerobic capacity and blood pressure in men with type 2 diabetes. However, the acute effects of REHIT on 24-h glycaemia have not been examined.Methods11 men with type 2 diabetes (mean ± SD: age, 52 ± 6 years; BMI, 29.7 ± 3.1 kg/m2; HbA1c, 7.0 ± 0.8%) participated in a randomised, four-trial crossover study, with continual interstitial glucose measurements captured during a 24-h dietary-standardised period following either (1) no exercise (CON); (2) 30 min of continuous exercise (MICT); (3) 10 × 1 min at ~ 90 HRmax (HIIT; time commitment, ~ 25 min); and (4) 2 × 20 s ‘all-out’ sprints (REHIT; time commitment, 10 min).ResultsCompared to CON, mean 24-h glucose was lower following REHIT (mean ± 95%CI: − 0.58 ± 0.41 mmol/L, p = 0.008, d = 0.55) and tended to be lower with MICT (− 0.37 ± 0.41 mmol/L, p = 0.08, d = 0.35), but was not significantly altered following HIIT (− 0.37 ± 0.59 mmol/L, p = 0.31, d = 0.35). This seemed to be largely driven by a lower glycaemic response (area under the curve) to dinner following both REHIT and MICT (− 11%, p  0.9 for both) but not HIIT (− 4%, p = 0.22, d = 0.38). Time in hyperglycaemia appeared to be reduced with all three exercise conditions compared with CON (REHIT: − 112 ± 63 min, p = 0.002, d = 0.50; MICT: -115 ± 127 min, p = 0.08, d = 0.50; HIIT − 125 ± 122 min, p = 0.04, d = 0.54), whilst indices of glycaemic variability were not significantly altered.ConclusionREHIT may offer a genuinely time-efficient exercise option for improving 24-h glycaemia in men with type 2 diabetes and warrants further study

The foreign body giant cell cannot resorb bone, but dissolves hydroxyapatite like osteoclasts

Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DCSTAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones-cytoskeletal organization that is considered to be osteoclast- specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme cathepsin K, which was hardly expressed by FBGCs. Functionally, the latter cells were able to dissolve a biomimetic hydroxyapatite coating in vitro, which was blocked by inhibiting v-ATPase enzyme activity. These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts. However, they are not able to digest the matrix fraction of bone, likely due to the lack of a ruffled border and cathepsin K

Degradation of Biomaterials

The tissue engineering approach requires suitable biomaterials to serve as three-dimensional scaffolds to support cell growth and differentiation into functional tissues. Depending on the type of tissue in need of repair, a biomaterial must be designed with specific performance criteria in mind. Several excellent books and review articles (e.g., Ratner et al. (2013), Temenoff and Mikos (2008)) on biomaterials have appeared. Essential characteristics of biomaterial scaffolds for tissue engineering applications are described by Williams (2014). For instance, biomaterials used as load-bearing prostheses for hips and knees should retain their mechanical function for the lifetime of the patient. In large bone defects, where load-bearing is not critical (e.g., the skull), biomaterials—used alone or with cells as tissue engineering constructs—need not be so mechanically strong (Chapter 10). In this case, a degradable biomaterial scaffold would be ideal to allow newly formed bone tissue to gradually take the place of the implanted construct resulting in seamless bone repair and no residual material. In this way, the manner in which the biomaterial is degraded—broken down in the body—is a primary consideration. When a biomaterial is implanted in the body, it is immediately exposed to physiologic fluid and shortly after, cells whose main purpose is to clear it from the host (Chapter 15). Thus, the degradation of biomaterials involves multiple physiologic processes at the same time making it a science to its own. This chapter reviews the degradation mechanisms of the two most established classes of biomaterials—ceramics and polymers—and how these degradation properties can be beneficial in their primary application, bone tissue engineering

Transmission electron microscopy of osteoclasts and FBGCs.

<p>In the osteoclast cultures, resorption pits were visible with exposed collagen fibrils protruding from the pit surface (<b>a</b>; white arrow). No resorption pits were seen in the FBGC cultures (<b>f;</b> red asterisk = bone). The osteoclasts showed an extensive ruffled border with on both sides a sealing zone (<b>b</b>; red asterisk, <b>c</b>; black arrow). No ruffled border was seen in the FBGCs (<b>f, g</b>). On the basolateral side of the membrane, both cell types showed “finger”-like structures (<b>b, g</b>; black arrow). For FBGCs, these membrane protrusions were generally longer and more abundant than those of osteoclasts. Adjacent to the FBGCs, an electron translucent area was seen covering the bone surface (<b>h</b>; red asterisk), suggesting demineralization. In this area, collagen fibils were exposed (<b>i</b>; white arrow). Both cell types contained high numbers of mitochondria (<b>b, c, g, i</b>; black) and the presence of a sealing zone approximatley 1 μm wide where no organelles were present (<b>e, j</b>; white arrow). Scale bar is 10 μm for panels <b>a</b> and <b>f</b>; 5 μm for panels <b>b</b> and <b>g</b>; 2 μm for panels <b>c</b> and <b>h</b>; and 1 μm for panels <b>d</b>, <b>e</b>, <b>i</b> and <b>j</b>.</p

Osteoclasts and FBGCs cultured on biomimetic hydroxyapatite coatings.

<p>After 25 days of culture, cells were stained for TRAcP activity and nuclei (DAPI). Multinucleated, TRAcP positive osteoclasts (<b>a</b>; black arrow) and FBGCs (<b>b</b>; black arrow) dissolved the coating (coating; red asterisk, plastic; black aterisk). Macrophages were also able to dissolve small parts of the coating (<b>c</b>; black arrow, <b>e</b>). Control wells, incubated without cells, showed no signs of apatite coating dissolution (<b>d</b>). Quantitatively, osteoclasts dissolved more of the coating than the FBGCs (<b>e</b>). Percent dissolution of the hydroxyapatite coating plots represent the mean ± S.D. per 0.32 cm² coating surface. Scale bar = 100 μm. *p<0.05, **p<0.01.</p

qPCR primer sequences.

<p>qPCR primer sequences.</p