bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
Authors: Bill Marie , B. van Kooten Niekerk Peter , S. Woll Petter , Laine Herborg Laura , Stidsholt Roug Anne , Hokland Peter , Nederby Line 
Published: February 2018

AbstractThe C‐type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia‐associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC12A on the earliest stem‐ and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors (CMPs) expressed CLEC12A, while for granulocyte‐macrophage progenitors and megakaryocyte‐erythroid progenitors (MEPs), the average percentages were 81.0% (95% CI [76.0;85.9]) and 11.9% (95% CI [9.3;14.6]), respectively. In line with the reduced CLEC12A expression on MEPs, functional assessment of purified CLEC12A+/− CMPs and MEPs in the colony‐forming unit assay demonstrated CLEC12A+ subsets to favour non‐erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC12A+ cell in the haematopoietic tree is the classically defined CMP. Furthermore, we show that CLEC12A‐expressing CMPs and MEPs are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC12A‐targeted therapy, and we propose CLEC12A to be included in future studies of myeloid cancer stem cell biology.
The mechanism for the radioprotective effects of zymosan‐A in mice
Authors: Du Jicong , Zhang Pei , Zhao Hainan , Dong Suhe , Yang Yanyong , Cui Jianguo , Gao Fu , Cai Jianming , Liu Cong 
Published: February 2018

AbstractIt proved that Zymosan‐A protected the haematopoietic system from radiation‐induced damage via Toll‐Like Receptor2 in our previous study. In this study, we investigated the potential mechanism for the radioprotective effects of Zymosan‐A. The mice were treated with Zymosan‐A (50 mg/kg, dissolved in NS) via peritoneal injection 24 and 2 hours before ionizing radiation. Apoptosis of bone marrow cells and the levels of IL‐6, IL‐12, G‐CSF and GM‐CSF were evaluated by flow cytometry assay. DNA damage was determined by γ‐H2AX foci assay. In addition, RNA sequencing was performed to identify differentially expressed genes (DEGs). Zymosan‐A protected bone marrow cells from radiation‐induced apoptosis, up‐regulated IL‐6, IL‐12, G‐CSF and GM‐CSF in bone marrow cells. Zymosan‐A also protected cells from radiation‐induced DNA damage. Moreover, RNA sequencing analysis revealed that Zymosan‐A induced 131 DEGs involved in the regulation of immune system process and inflammatory response. The DEGs were mainly clustered in 18 KEGG pathways which were also associated with immune system processes. Zymosan‐A protected bone marrow cells from radiation‐induced apoptosis and up‐regulated IL‐6, IL‐12, G‐CSF and GM‐CSF. Moreover, Zymosan‐A might also exhibit radioprotective effects through regulating immune system process and inflammatory response. These results provided new knowledge regarding the radioprotective effect of Zymosan‐A.
Regulation of insulin resistance and type II diabetes by hepatitis C virus infection: A driver function of circulating miRNAs
Authors: Singhal Adit , Agrawal Aniruddh , Ling Jun 
Published: February 2018

AbstractHepatitis C virus (HCV) infection is a serious worldwide healthcare issue. Its association with various liver diseases including hepatocellular carcinoma (HCC) is well studied. However, the study on the relationship between HCV infection and the development of insulin resistance and diabetes is very limited. Current research has already elucidated some underlying mechanisms, especially on the regulation of metabolism and insulin signalling by viral proteins. More studies have emerged recently on the correlation between HCV infection‐derived miRNAs and diabetes and insulin resistance. However, no studies have been carried out to directly address if these miRNAs, especially circulating miRNAs, have causal effects on the development of insulin resistance and diabetes. Here, we proposed a new perspective that circulating miRNAs can perform regulatory functions to modulate gene expression in peripheral tissues leading to insulin resistance and diabetes, rather than just a passive factor associated with these pathological processes. The detailed rationales were elaborated through comprehensive literature review and bioinformatic analyses. miR‐122 was identified to be one of the most potential circulating miRNAs to cause insulin resistance. This result along with the idea about the driver function of circulating miRNAs will promote further investigations that eventually lead to the development of novel strategies to treat HCV infection‐associated extrahepatic comorbidities.
Neural androgen receptors affect the number of surviving new neurones in the adult dentate gyrus of male mice
Authors: Swift‐Gallant A. , Duarte‐Guterman P. , Hamson D. K. , Ibrahim M. , Monks D. A. , Galea L. A. M. 
Published: February 2018

Adult hippocampal neurogenesis occurs in many mammalian species. In rats, the survival of new neurones within the hippocampus is modulated by the action of androgen via the androgen receptor (AR); however, it is not known whether this holds true in mice. Furthermore, the evidence is mixed regarding whether androgens act in neural tissue or via peripheral non‐neural targets to promote new neurone survival in the hippocampus. We evaluated whether the action of androgen via AR underlies the survival of new neurones in mice, and investigated whether increasing AR selectively in neural tissue would increase new neurone survival in the hippocampus. We used the cre‐loxP system to overexpress AR only in neural tissues (Nestin‐AR). These males were compared with wild‐type males, as well as control males with 1 of the 2 mutations required for overexpression. Mice were gonadectomised and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU) and for 37 days (following BrdU injection), mice were treated with oil or dihydrotestosterone (DHT). Using immunohistochemistry, proliferation (Ki67) and survival (BrdU) of new neurones were both evaluated in the dorsal and ventral dentate gyrus. Dihydrotestosterone treatment increased the survival of new neurones in the entire hippocampus in wild‐type mice and control mice that only have 1 of 2 necessary mutations for transgenic expression. However, DHT treatment did not increase the survival of new neurones in mice that overexpressed AR in neural tissue. Cell proliferation (Ki67) and cell death (pyknotic cells) were not affected by DHT treatment in wild‐type or transgenic males. These results suggest that androgens act via neural AR to affect hippocampal neurogenesis by promoting cell survival; however, the relationship between androgen dose and new neurone survival is nonlinear.
3D quantitative comparative analysis of long bone diaphysis variations in microanatomy and cross‐sectional geometry
Authors: Houssaye Alexandra , Taverne Maxime , Cornette Raphaël 
Published: February 2018

AbstractLong bone inner structure and cross‐sectional geometry display a strong functional signal, leading to convergences, and are widely analyzed in comparative anatomy at small and large taxonomic scales. Long bone microanatomical studies have essentially been conducted on transverse sections but also on a few longitudinal ones. Recent studies highlighted the interest in analyzing variations of the inner structure along the diaphysis using a qualitative as well as a quantitative approach. With the development of microtomography, it has become possible to study three‐dimensional (3D) bone microanatomy and, in more detail, the form–function relationships of these features. This study focused on the selection of quantitative parameters to describe in detail the cross‐sectional shape changes and distribution of the osseous tissue along the diaphysis. Two‐dimensional (2D) virtual transverse sections were also performed in the two usual reference planes and results were compared with those obtained based on the whole diaphysis analysis. The sample consisted in 14 humeri and 14 femora of various mammalian taxa that are essentially terrestrial. Comparative quantitative analyses between different datasets made it possible to highlight the parameters that are strongly impacted by size and phylogeny and the redundant ones, and thus to estimate their relevance for use in form‐function analyses. The analysis illustrated that results based on 2D transverse sections are similar for both sectional planes; thus if a strong bias exists when mixing sections from the two reference planes in the same analysis, it would not problematic to use either one plane or the other in comparative studies. However, this may no longer hold for taxa showing a much stronger variation in bone microstructure along the diaphysis. Finally, the analysis demonstrated the significant contribution of the parameters describing variations along the diaphysis, and thus the interest in performing 3D analyses; this should be even more fruitful for heterogeneous diaphyses. In addition, covariation analyses showed that there is a strong interest in removing the size effect to access the differences in the microstructure of the humerus and femur. This methodological study provides a reference for future quantitative analyses on long bone inner structure and should make it possible, through a detailed knowledge of each descriptive parameter, to better interpret results from the multivariate analyses associated with these studies. This will have direct implications for studies in vertebrate anatomy, but also in paleontology and anthropology.
Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells
Authors: Ren Boxue , Li Defang , Si Lingling , Ding Yangfang , Han Jichun , Chen Xiaoyu , Zheng Qiusheng 
Published: February 2018

Abstract

Objective
Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells.

Methods
After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR.

Key findings
Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased.

Conclusions
Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation.
Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF‐1α‐VEGF pathway in oxygen‐induced retinopathy mice
Authors: Xu Yue , Lu Xi , Hu Yaguang , Yang Boyu , Tsui Ching‐Kit , Yu Shanshan , Lu Lin , Liang Xiaoling 
Published: February 2018

AbstractRetinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti‐VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti‐angiogenic and neuroglial protective in the progression of ROP remains unknown. Thus, this study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen‐induced retinopathy (OIR) mice. The results showed a reduction in retinal vascular leakage in OIR mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen‐induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, HIF‐1α‐VEGF pathway was activated in the retina of OIR mice, yet was suppressed in melatonin‐treated OIR mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti‐inflammation effect via inhibition of HIF‐1α‐VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP.
Victorian literature and archaeology: Contemporary excavations
Authors: Blumberg Angie 
Published: February 2018

AbstractThis article surveys recent scholarship tracing archaeological discourse in Victorian literature. While scholars in the past two decades have produced many valuable works investigating the Victorian literature of science, archaeology's disciplinary fluidity and infancy in the 19th century have relegated it often to a marginal place in studies of imperialism, museum culture, or limited to brief mentions in studies of Victorian Hellenism or Egyptology. Recent work, however, locates archaeology at the center of Victorian literary explorations of gender, sexuality, material culture, temporality, and aesthetic form. Tracing many of these studies, and suggesting future directions for scholarship, this essay reveals how Victorian writers turned to archaeology to understand themselves and their modernity.
Assessing niche partitioning of co‐occurring sibling bat species by DNA metabarcoding
Authors: Arrizabalaga‐Escudero Aitor , Clare Elizabeth L. , Salsamendi Egoitz , Alberdi Antton , Garin Inazio , Aihartza Joxerra , Goiti Urtzi 
Published: February 2018

AbstractNiche partitioning through foraging is a mechanism likely involved in facilitating the coexistence of ecologically similar and co‐occurring animal species by separating their use of resources. Yet, this mechanism is not well understood in flying insectivorous animals. This is particularly true of bats, where many ecologically similar or cryptic species coexist. The detailed analysis of the foraging niche in sympatric, cryptic sibling species provides an excellent framework to disentangle the role of specific niche factors likely involved in facilitating coexistence. We used DNA metabarcoding to determine the prey species consumed by a population of sympatric sibling Rhinolophus euryale and Rhinolophus mehelyi whose use of habitat in both sympatric and allopatric ranges has been well established through radio tracking. Although some subtle dietary differences exist in prey species composition, the diet of both bats greatly overlapped (Ojk = 0.83) due to the consumption of the same common and widespread moths. Those dietary differences we did detect might be related to divergences in prey availabilities among foraging habitats, which prior radio tracking on the same population showed are differentially used and selected when both species co‐occur. This minor dietary segregation in sympatry may be the result of foraging on the same prey‐types and could contribute to reduce potential competitive interactions (e.g., for prey, acoustic space). Our results highlight the need to evaluate the spatial niche dimension in mediating the co‐occurrence of similar insectivorous bat species, a niche factor likely involved in processes of bat species coexistence.
Chromosomal inversions promote genomic islands of concerted evolution of Hsp70 genes in the Drosophila subobscura species subgroup
Authors: Puig Giribets Marta , García Guerreiro María Pilar , Santos Mauro , Ayala Francisco J. , Tarrío Rosa , Rodríguez‐Trelles Francisco 
Published: February 2018

AbstractHeat‐shock (HS) assays to understand the connection between standing inversion variation and evolutionary response to climate change in Drosophila subobscura found that “warm‐climate” inversion O3+4 exhibits non‐HS levels of Hsp70 protein like those of “cold‐climate” OST after HS induction. This was unexpected, as overexpression of Hsp70 can incur multiple fitness costs. To understand the genetic basis of this finding, we have determined the genomic sequence organization of the Hsp70 family in four different inversions, including OST, O3+4, O3+4+8 and O3+4+16, using as outgroups the remainder of the subobscura species subgroup, namely Drosophila madeirensis and Drosophila guanche. We found (i) in all the assayed lines, the Hsp70 family resides in cytological locus 94A and consists of only two genes, each with four HS elements (HSEs) and three GAGA sites on its promoter. Yet, in OST, the family is comparatively more compact; (ii) the two Hsp70 copies evolve in concert through gene conversion, except in D. guanche; (iii) within D. subobscura, the rate of concerted evolution is strongly structured by inversion, being higher in OST than in O3+4; and (iv) in D. guanche, the two copies accumulated multiple differences, including a newly evolved “gap‐type” HSE2. The absence of concerted evolution in this species may be related to a long‐gone‐unnoticed observation that it lacks Hsp70 HS response, perhaps because it has evolved within a narrow thermal range in an oceanic island. Our results point to a previously unrealized link between inversions and concerted evolution, with potentially major implications for understanding genome evolution.
A novel experimental system using the liverwort Marchantia polymorpha and its fungal endophytes reveals diverse and context‐dependent effects
Authors: Nelson Jessica M. , Hauser Duncan A. , Hinson Rosemary , Shaw A. Jonathan 
Published: February 2018

Summary

Fungal symbioses are ubiquitous in plants, but their effects have mostly been studied in seed plants. This study aimed to assess the diversity of fungal endophyte effects in a bryophyte and identify factors contributing to the variability of outcomes in these interactions.

Fungal endophyte cultures and axenic liverwort clones were isolated from wild populations of the liverwort, Marchantia polymorpha. These collections were combined in a gnotobiotic system to test the effects of fungal isolates on the growth rates of hosts under laboratory conditions.

Under the experimental conditions, fungi isolated from M. polymorpha ranged from aggressively pathogenic to strongly growth‐promoting, but the majority of isolates caused no detectable change in host growth. Growth promotion by selected fungi depended on nutrient concentrations and was inhibited by coinoculation with multiple fungi.

The M. polymorpha endophyte system expands the resources for this model liverwort. The experiments presented here demonstrate a wealth of diversity in fungal interactions even in a host reported to lack standard mycorrhizal symbiosis. In addition, they show that some known pathogens of vascular plants live in M. polymorpha and can confer benefits to this nonvascular host. This highlights the importance of studying endophyte effects across the plant tree of life.
Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment
Authors: Coello‐Suanzes JA , Rollon‐Ugalde V , Castaño‐Seiquer A , Lledo‐Villar E , Herce‐Lopez J , Infante‐Cossio P , Rollon‐Mayordomo A 
Published: February 2018

ObjectiveTo evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate‐related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA).Materials and MethodsThis single‐center clinical study included 255 patients with cancer monitored over a 6‐year period. Patients received dental treatment prior to (group A) or after (group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP), and incidence rate (IR) in both groups were analyzed using significance tests. BRONJ onset was estimated using the Kaplan–Meier estimator and log‐rank test. Independent risk factors to develop BRONJ were evaluated using Cox regression analysis models.ResultsThirty‐seven patients suffered from BRONJ (IP = 14.5%), 7.3% in group A and 36.5% in group B (p = .000). The IR was 0.007 patients/month in group B and 0.004 in group A. BRONJ‐free survival at 3 years was 97% in group A and 66% in group B. Survival curves were significant (p = .056) according to log‐rank test. Multivariate Cox models showed that dental extractions (p = .000) were significant.ConclusionsBRONJ occurred significantly in patients who underwent dental extractions after the initiation of ZA and did not accomplish a preventive dental program.
Epidemiology and outcome of chronic high Epstein‐Barr viral load carriage in pediatric kidney transplant recipients
Authors: Yamada Masaki , Nguyen Christina , Fadakar Paul , Ganoza Armando , Humar Abhinav , Shapiro Ron , Michaels Marian G. , Green Michael 
Published: February 2018

AbstractThe development of EBV infection and PTLD is normally associated with a high EBV viral load in peripheral blood. Observations have previously identified existence of a CHL carrier state that demonstrated variable outcomes based upon the organ which was transplanted. Data defining the incidence and outcome of CHL in pediatric KTx are not well described. The charts of children undergoing isolated KTx at Children's Hospital of Pittsburgh between January 2000 and December 2014 were retrospectively reviewed. EBV loads in the peripheral blood were routinely measured as part of surveillance protocols at our center. CHL was defined as the presence of high load for >50% of samples for ≥6 months. PTLD was defined histologically using WHO definitions. Of 188 isolated KTx recipients, we identified a total of 16 (8%) children who developed CHL carrier state. No patient developed EBV‐driven late‐onset PTLD. Age at the time of KTx was significantly lower in the CHL group (median 3.9 years, interquartile range: IQR 2.9‐6.6, P = .0004). Children in the CHL group were more likely to be EBV‐seronegative prior to KTx (94%, 15/16), compared to the UVL and LVL groups (55% and 50%, respectively, P < .002). The median duration of CHL carrier state was 20 months (IQR 10.7‐35.8). Fifteen of the 16 CHL carriers experienced spontaneous resolution of CHL carrier state. Children in the CHL group were younger at the time of primary EBV infection (P = .023). Finally, antiviral medication was not effective in either preventing or decreasing the EBV viral load in blood (P = .84). Overall incidence of late‐onset PTLD is very low compared to heart and intestinal transplant, even though KTx recipients can develop CHL carrier state. The CHL carriers in KTx recipients were EBV‐seronegative prior to transplant and were younger both at the time of KTx and at the time of primary EBV infection compared to those in the UVL and HVL groups. Antivirals did not prevent EBV infection or decrease EBV viral loads.