bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of piRNAs and piRNA clusters in the testes of the Mongolian horse
Authors: Li Bei , He Xiaolong , Zhao Yiping , Bai Dongyi , Bou Gerelchimeg , Zhang Xinzhuang , Su Shaofeng , Dao Leng , Liu Rui , Wang Yuejiao , Manglai Dugarjaviin 
Published: March 2019

AbstractP-element induced wimpy testis-interacting RNAs (piRNAs) are essential for testicular development and spermatogenesis in mammals. Comparative analyses of the molecular mechanisms of spermatogenesis among different organisms are therefore dependent on accurate characterizations of piRNAs. At present, little is known of piRNAs in non-model organisms. Here, we characterize piRNAs in the Mongolian horse, a hardy breed that reproduces under extreme circumstances. A thorough understanding of spermatogenesis and reproduction in this breed may provide insights for the improvement of fecundity and reproductive success in other breeds. We identified 4,936,717 piRNAs and 7,890 piRNA clusters across both testicular developmental stages. Of these, 2,236,377 putative piRNAs were expressed in the mature samples only, and 2,391,271 putative piRNAs were expressed in the immature samples only. Approximately 3,016 piRNA clusters were upregulated in the mature testes as compared to the immature testes, and 4,874 piRNA clusters were downregulated. Functional and pathway analyses indicated that the candidate generating genes of the predicted piRNAs were likely involved in testicular development and spermatogenesis. Our results thus provide information about differential expression patterns in genes associated with testicular development and spermatogenesis in a non-model animal.
Greater brain activity during the resting state and the control of activation during the performance of tasks
Authors: Huang Jie 
Published: March 2019

AbstractThe brain’s operations are mainly intrinsic, involving the acquisition and maintenance of information for interpreting, responding to and predicting environmental demands. The brain’s on-going intrinsic activity (i.e., the resting-state activity) is spontaneous, but this spontaneous activity exhibits a surprising level of spatial and temporal organization across the whole brain. In this study we compared the intrinsic activity with the activity evoked by tasks, and made the comparison at several levels of analysis from a finger-tapping-activated area within the primary sensorimotor cortex to the whole brain. We found that, contrary to our intuition, the intrinsic activity was substantially larger than the task activity and consistently so for all levels of analysis. For the task state, the brain: (1) controlled the intrinsic activity not only during the performance of a task but also during the rest between tasks; (2) activated a task-specific network only when the task was performed but kept it relatively “silent” for other different tasks; and (3) simultaneously controlled the activation of all task-specific networks during the performance of each task.
Using science to sell apps: Evaluation of mental health app store quality claims
Authors: Larsen Mark Erik , Huckvale Kit , Nicholas Jennifer , Torous John , Birrell Louise , Li Emily , Reda Bill 
Published: March 2019

AbstractDespite the emergence of curated app libraries for mental health apps, personal searches by consumers remain a common method for discovering apps. App store descriptions therefore represent a key channel to inform consumer choice. This study examined the claims invoked through these app store descriptions, the extent to which scientific language is used to support such claims, and the corresponding evidence in the literature. Google Play and iTunes were searched for apps related to depression, self-harm, substance use, anxiety, and schizophrenia. The descriptions of the top-ranking, consumer-focused apps were coded to identify claims of acceptability and effectiveness, and forms of supporting statement. For apps which invoked ostensibly scientific principles, a literature search was conducted to assess their credibility. Seventy-three apps were coded, and the majority (64%) claimed effectiveness at diagnosing a mental health condition, or improving symptoms, mood or self-management. Scientific language was most frequently used to support these effectiveness claims (44%), although this included techniques not validated by literature searches (8/24 = 33%). Two apps described low-quality, primary evidence to support the use of the app. Only one app included a citation to published literature. A minority of apps (14%) described design or development involving lived experience, and none referenced certification or accreditation processes such as app libraries. Scientific language was the most frequently invoked form of support for use of mental health apps; however, high-quality evidence is not commonly described. Improved knowledge translation strategies may improve the adoption of other strategies, such as certification or lived experience co-design.
Dynamic host immune response in virus-associated cancers
Authors: Cao Song , Wylie Kristine M. , Wyczalkowski Matt A. , Karpova Alla , Ley Jessica , Sun Sam , Mashl R. Jay , Liang Wen-Wei , Wang Xiaowei , Johnson Kimberly , DiPersio John F. , Gay Hiram , Ratner Lee , Chen Feng , Adkins Douglas R. , Ding Li 
Published: March 2019

AbstractViruses drive carcinogenesis in human cancers through diverse mechanisms that have not been fully elucidated but include promoting immune escape. Here we investigated associations between virus-positivity and immune pathway alteration for 2009 tumors across six virus-related cancer types. Analysis revealed that for 3 of 72 human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSC) the HPV genome integrated in immune checkpoint genes PD-L1 or PD-L2, driving elevated expression in the corresponding gene. In addition to the previously described upregulation of the PD-1 immunosuppressive pathway in Epstein-Barr virus (EBV)-positive stomach tumors, we also observed upregulation of the PD-1 pathway in cytomegalovirus (CMV)-positive tumors. Furthermore, we found signatures of T-cell and B-cell response in HPV-positive HNSC and EBV-positive stomach tumors and HPV-positive HNSC patients were associated with better survival when T-cell signals were detected. Our work reveals that viral infection may recruit immune effector cells, and upregulate PD-1 and CTLA-4 immunosuppressive pathways.
Rivastigmine and metabolite analogues with putative Alzheimer’s disease-modifying properties in a Caenorhabditis elegans model
Authors: Dighe Satish N. , De la Mora Eugenio , Chan Stephen , Kantham Srinivas , McColl Gawain , Miles Jared A. , Veliyath Suresh Kumar , Sreenivas B. Yogi , Nassar Zeyad D. , Silman Israel , Sussman Joel L. , Weik Martin , McGeary Ross P. , Parat Marie-Odile , Brazzolotto Xavier , Ross Benjamin P. 
Published: March 2019

AbstractThe development of polyphenols as drugs for Alzheimer’s disease (AD) is thwarted by their meagre brain availability due to instability and poor druglikeness. Here we describe the successful development of stable, druglike polyphenolic analogues of the current AD drug rivastigmine, that have high apparent blood-brain barrier permeabilities and multifunctional properties for AD treatment. The compounds inhibit cholinesterases and amyloid beta (Aβ) fibrillation, protect against Aβ42-induced toxicity in vitro, and demonstrate efficacy in vivo in a transgenic Caenorhabditis elegans model expressing Aβ42, with potencies similar to rivastigmine and natural polyphenols. The results suggest that a tertiary amine substituent is amenable for developing water-soluble, membrane-permeable polyphenols, and its incorporation adjacent to a hydroxy group is favourable for intramolecular hydrogen bonding that facilitates membrane permeability. Carbamylation of one hydroxy group protects the polyphenols from degradation and mostly improves their membrane permeability. These design strategies may assist in the development of polyphenol-based drugs.
The DCBLD receptor family: emerging signaling roles in development, homeostasis and disease
Authors: Schmoker Anna M. , Ebert Alicia M. , Ballif Bryan A. 
Published: March 2019

AbstractThe discoidin, CUB, and LCCL domain-containing (DCBLD) receptor family are composed of the type-I transmembrane proteins DCBLD1 and DCBLD2 (also ESDN and CLCP1). These proteins are highly conserved across vertebrates and possess similar domain structure to that of neuropilins, which act as critical co-receptors in developmental processes. Although DCBLD1 remains largely uncharacterized, the functional and mechanistic roles of DCBLD2 are emerging. This review provides a comprehensive discussion of this presumed receptor family, ranging from structural and signaling aspects to their associations with cancer, physiology, and development.
Acute haemodynamic changes during haemodialysis do not exacerbate gut hyperpermeability
Authors: Wong Jonathan , Lenaerts Kaatje , Meesters Dennis M. , Olde Damink Steven W.M. , van Eijk Hans M.H. , Vilar Enric , Farrington Ken 
Published: March 2019

Abstract
Introduction: The gastrointestinal tract is a potential source of inflammation in dialysis patients. In vitro studies suggest breakdown of the gut barrier in uraemia leading to increased intestinal permeability and it is hypothesised that haemodialysis exacerbates this problem due to mesenteric ischaemia induced by blood volume changes during treatment.
Method: The effect of haemodialysis on intestinal permeability was studied in ten haemodialysis patients and compared with five controls. Intestinal permeability was assessed by measuring the differential absorption of four orally administered sugar probes which provides an index of small and whole bowel permeability. A multi-sugar solution (containing lactulose, rhamnose, sucralose and erythritol) was orally administered after an overnight fast. Plasma levels of all sugar probes were measured hourly for 10 h post-administration. In haemodialysis patients, the procedure was carried out twice — once on a non-dialysis day and once immediately after haemodialysis.
Results: Area under curve (AUC) for lactulose:rhamnose (L:R) ratio and sucralose:erythritol (S:E) ratio was similar post-dialysis and on non-dialysis days. AUC for L:R was higher in haemodialysis patients compared with controls (0.071 vs. 0.034, P=0.001), AUC for S:E ratio was not significantly different. Levels of lactulose, sucralose and erythritol were elevated and retained longer in haemodialysis patients compared with controls due to dependence of sugars on kidney function for clearance.
Conclusion: We found no significant acute changes in intestinal permeability in relation to the haemodialysis procedure. Valid comparison of intestinal permeability between controls and haemodialysis patients was not possible due to the strong influence of kidney function on sugar levels.
LincRNA-p21 suppresses glutamine catabolism and bladder cancer cell growth through inhibiting glutaminase expression
Authors: Zhou Qun , Zhan Hengji , Lin Fan , Liu Yuhan , Yang Kang , Gao Qunjun , Ding Mengting , Liu Yuchen , Huang Weiren , Cai Zhiming 
Published: March 2019

Abstract
Long intergenic non-coding RNA p21 (lincRNA-p21) is down-regulated in some solid tumors. Glutamine catabolism plays an important role in cancer development. However, the role of lincRNA-p21 and its association with glutamine catabolism remain unknown in bladder cancer (BC). In the present study, we investigated the involvement of lincRNA-p21 and glutamine catabolism in BC cell growth and found that ectopic linRNA-p21 expression reduced the proliferation and growth of BIU87 and 5637 cells. Opposite results were observed in lincRNA-p21 silenced J82 and T24 cells. The expression of glutaminase (GLS), intracellular level of glutamate and α-Ketoglutarate (α-KG) were negatively regulated by lincRNA-p21. GLS overexpression reversed the suppressive function of lincRNA-p21 on BC cell growth and proliferation. In contrast, GLS reduction by siRNA blunted the viability of lincRNA-p21 lowly expressed BC cells. Furthermore, lincRNA-p21 and GLS abundance dictated the sensitivity of BC cells to bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) treatment. Importantly, reduced lincRNA-p21 expression and increased GLS mRNA level were observed in BC tissues compared with the normal tissues. Our results demonstrate that lincRNA-p21 suppresses the BC cell growth through inhibiting GLS and glutamine catabolism. Targeting this cascade may be a promising treatment strategy for BC patients.
Discussion of relationships among changes of pathological indicators, postoperative lymphedema of the upper limb, and prognosis of patients with breast cancer
Authors: Zhang Xiping , Tang Binbin , Zou Dehong , Yang Hongjian , Qiao Enqi , He Xiangming , Yu Feijiang 
Published: March 2019

Abstract
Objectives: The present study aimed to discuss the impacts of changes to pathological indicators of patients with breast cancer upon the incidence of postoperative lymphedema of the upper limb and prognosis. Methods: 2597 female patients with breast cancer who received surgical treatment in our hospital were enrolled in the present study to evaluate the incidence of these patients’ postoperative lymphedema of the upper limb. Results: For patients with breast cancer, the incidence of postoperative lymphedema of the upper limb was related to T stage of breast cancer, lymph node metastasis, the number of metastatic lymph nodes, pTNM stage, and pathological types of breast cancer (P&lt;0.05). Lymph node metastasis was an independent risk factor of lymphedema of the upper limb; lymph node metastasis and Ki-67 expression level were independent factors that impacted pathologic complete response rate of neoadjuvant chemotherapies. Patients’ mortality was correlated to pathological and molecular subtypes, Ki-67 expression level, ER expression level, PR expression level, and pTNM stage (P&lt;0.05), among which the pTNM stage, Ki-67 expression level, and PR expression level were independent factors that affected prognosis of patients with breast cancer. Conclusion: Patients with lymph node metastasis were more prone to lymphedema of the upper limb, while it was easier for those whose Ki-67 expression level was high and who were not subject to lymph node metastasis to get a pathological complete response after receiving neoadjuvant chemotherapies. The prognosis was poorer among patients whose progesterone receptors were negative and Ki-67 expression levels were high at the advanced pTNM stage.
Recruited lysosomal enzymes as major digestive enzymes in insects
Authors: Terra Walter R. , Dias Renata O. , Ferreira Clélia 
Published: March 2019

Abstract
The mass recruitment to the midgut contents of lysosomal proteolytic enzymes occurred in insects under three major selective pressures. Hemipteran (true bugs, aphids, and cicadas) ancestors lost their serine peptidases (SP) on adapting to feed on protein-free plant sap. When they returned to protein diets, their cathepsins L and B were recruited to replace their lost SP. Among beetles of the series Cucujiformia, cathepsins L were recruited to hydrolyze ingested plant inhibitors that affect their major SP and/or to deal with special seed proteins, such as prolamins. Larval flies have a very acid middle midgut and use cathepsin D to digest bacteria from their infected food. All the recruited enzymes originated from duplicated genes. The recruited digestive enzymes differ from their lysosomal counterparts in critical regions of their amino acid sequences that resulted in changes in substrate specificities and other kinetic properties. The discharge of digestive cathepsins in the midgut contents, instead of lysosomes, seems to be a consequence of their overexpression or the existence of new targeting signals. Their activation at the midgut contents occurs by an autoactivation mechanism or with the help of other enzymes or by a combination of both. The targeting to lysosomes of the insect lysosomal enzymes does not follow the mammalian mannose 6-phosphate route, but an incompletely known mechanism.
Protein engineering: the potential of remote mutations
Authors: Wilding Matthew , Hong Nansook , Spence Matthew , Buckle Ashley M. , Jackson Colin J. 
Published: March 2019

Abstract
Engineered proteins, especially enzymes, are now commonly used in many industries owing to their catalytic power, specific binding of ligands, and properties as materials and food additives. As the number of potential uses for engineered proteins has increased, the interest in engineering or designing proteins to have greater stability, activity and specificity has increased in turn. With any rational engineering or design pursuit, the success of these endeavours relies on our fundamental understanding of the systems themselves; in the case of proteins, their structure–dynamics–function relationships. Proteins are most commonly rationally engineered by targeting the residues that we understand to be functionally important, such as enzyme active sites or ligand-binding sites. This means that the majority of the protein, i.e. regions remote from the active- or ligand-binding site, is often ignored. However, there is a growing body of literature that reports on, and rationalises, the successful engineering of proteins at remote sites. This minireview will discuss the current state of the art in protein engineering, with a particular focus on engineering regions that are remote from active- or ligand-binding sites. As the use of protein technologies expands, exploiting the potential improvements made possible through modifying remote regions will become vital if we are to realise the full potential of protein engineering and design.
Cell-surface translocation of annexin A2 contributes to bleomycin-induced pulmonary fibrosis by mediating inflammatory response in mice
Authors: Lei Yunlong , Wang Kui , Li Xuefeng , Li Yi , Feng Xuping , Zhou Jing , Zhang Zhe , Huang Canhua , Zhang Tao 
Published: March 2019

AbstractBleomycin, a widely used anti-cancer drug, may give rise to pulmonary fibrosis, a serious side effect which is associated with significant morbidity and mortality. Despite the intensive efforts, the precise pathogenic mechanisms of pulmonary fibrosis still remain to be clarified. Our previous study showed that bleomycin bound directly to annexin A2 (ANXA2, or p36), leading to development of pulmonary fibrosis by impeding transcription factor EB (TFEB)-induced autophagic flux. Here, we demonstrated that ANXA2 also played a critical role in bleomycin-induced inflammation, which represents another major cause of bleomycin-induced pulmonary fibrosis. We found that bleomycin could induce the cell surface translocation of ANXA2 in lung epithelial cells through exosomal secretion, associated with enhanced interaction between ANXA2 and p11. Knockdown of ANXA2 or blocking membrane ANXA2 mitigated bleomycin-induced activation of nuclear factor (NF)-κB pathway and production of pro-inflammatory cytokine IL-6 in lung epithelial cells. ANXA2-deficient (ANXA2−/−) mice treated with bleomycin exhibit reduced pulmonary fibrosis along with decreased cytokine production compared with bleomycin-challenged wild-type mice. Further, the surface ANXA2 inhibitor TM601 could ameliorate fibrotic and inflammatory response in bleomycin-treated mice. Taken together, our results indicated that, in addition to disturbing autophagic flux, ANXA2 can contribute to bleomycin-induced pulmonary fibrosis by mediating inflammatory response.
Use of the immunoglobulin G avidity assay to differentiate between recent Zika and past dengue virus infections
Authors: Furuya Andrea K.M. , Hunt Danielle , George Kirsten St. , Dupuis Alan P. , Kramer Laura D. , Shi Pei-Yong , Wong Susan 
Published: March 2019

Abstract
Zika (ZIKV) and dengue (DENV) virus infections elicit a robust but cross-reactive antibody response against the viral envelope protein, while antibody responses against non-structural proteins (NS) are more virus specific. Building on this premise, we have previously developed a flavivirus multiplex microsphere immunoassay (MIA) for the serologic diagnosis of ZIKV and DENV infections. This assay significantly improved diagnostic accuracy; however, MIA could not differentiate more recent from past infections, which still represents a major diagnostic challenge. Therefore, an immunoglobulin G (IgG) based avidity assay was developed and its diagnostic performance evaluated. Specimens from New York State residents were submitted to the Wadsworth Center New York State Department of Health (NYSDOH) for routine clinical testing by Zika IgM ELISA and plaque reduction neutralization test (PRNT). Using our previously developed flavivirus MIA as a platform, we developed an IgG avidity assay to discriminate recent ZIKV from past DENV infections. Zika IgM positive specimens had an average Zika IgG avidity index of 14.8% (95% CI: 11.0–18.4%), while Zika IgM negative but flavivirus MIA and PRNT positive samples had an average Zika IgG avidity index of 34.9% (95% CI: 31.1–38.7%). Specimens positive for dengue antibodies by flavivirus MIA and PRNT had an average dengue IgG avidity index of 68.7% (95% CI: 62.7–75.0%). The IgG avidity assay accurately distinguished recent ZIKV from past DENV infections in patients who traveled to dengue endemic regions. This assay could be very useful in patients with high risk of Zika complications such as pregnant women and monitoring immune responses in vaccine trials.
High‐efficiency soft‐switching step‐up DC–DC converter derived from a synchronous boost converter
Authors: Lee Sin‐Woo , Do Hyun‐Lark 
Published: March 2019

This study presents a high‐efficiency soft‐switching step‐up DC–DC converter. The proposed converter achieves zero‐voltage switching of power switches and zero‐current switching of the output diode. Also, it has improved the voltage conversion ratio. Moreover, the switch voltage stress can be lowered than the output voltage. Hence, improved efficiency, especially at full load, is achieved. The operational principle and detailed analysis of the proposed converter are given. The performance of the proposed converter is verified by testing a prototype converter implemented in the laboratory on an output 200 V–200 W.
Microstructure of injection moulding machine mould clamping mechanism: design and motion simulation
Authors: Jin Zhiming , Zhang Yajun , Wang Xinliang , Williams Jacob , Liu Zhen , Huang Zhongyuan , Falkner D'Lauren , Zhou Gang , Dong Liqun , Zhuang Jian , Wang Zhe 
Published: March 2019

With the advent of intelligence technologies, more and more machines and devices are involved in the creation of complex structures. In the intelligent manufacturing industries, mouldings including injection moulding, blow moulding, compression moulding, and others play critical roles in manufacturing highly precise parts required for building intelligent machines (such as computers, cell phones, robots etc.). The performance of the clamping mechanism directly affects the quality of the microstructure of injection products. The design of the injection moulding mould clamping mechanism is based on the microstructure characteristics of the trip of the toggle lever mechanism ratio, speed ratio, and force amplification ratio. These are used to study the main performance parameters, such as analysis, as well as for the establishment of the physical model of the clamping mechanism. The model is based on the microstructure of injection of hyperbolic elbow clamping mechanism kinematics simulation. Simulation results and theoretical calculation contrast analysis show that the maximum dynamic template speed is 215.34 mm/s. The dynamic templates and cross‐head speed ratio is 2.15; therefore, the design of the injection moulding mould clamping mechanism for the microstructure provides favourable technical support. The method described here is important to build complicated moulds required to build highly precise parts to build intelligent machineries.