bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC in Germinal Center‐derived lymphomas: Mechanisms and therapeutic opportunities
Authors: Bisso Andrea , Sabò Arianna , Amati Bruno 
Published: March 2019

SummaryThe rearrangement of immunoglobulin loci during the germinal center reaction is associated with an increased risk of chromosomal translocations that activate oncogenes such as MYC, BCL2 or BCL6, thus contributing to the development of B‐cell lymphomas. MYC and BCL2 activation are initiating events in Burkitt's (BL) and Follicular Lymphoma (FL), respectively, but can occur at later stages in other subtypes such as Diffuse Large‐B Cell Lymphoma (DLBCL). MYC can also be activated during the progression of FL to the transformed stage. Thus, either DLBCL or FL can give rise to aggressive double‐hit lymphomas (DHL) with concurrent activation of MYC and BCL2. Research over the last three decades has improved our understanding of the functions of these oncogenes and the basis for their cooperative action in lymphomagenesis. MYC, in particular, is a transcription factor that contributes to cell activation, growth and proliferation, while concomitantly sensitizing cells to apoptosis, the latter being blocked by BCL2. Here, we review our current knowledge about the role of MYC in germinal center B‐cells and lymphomas, discuss MYC‐induced dependencies that can sensitize cancer cells to select pharmacological inhibitors, and illustrate their therapeutic potential in aggressive lymphomas—and in particular in DHL, in combination with BCL2 inhibitors.
MicroRNA‐mediated regulation of T follicular helper and T follicular regulatory cell identity
Authors: Maul Julia , Alterauge Dominik , Baumjohann Dirk 
Published: March 2019

SummaryT follicular helper (Tfh) cells are critical mediators of germinal center (GC) formation and essential for potent humoral immunity. In contrast, T follicular regulatory (Tfr) cells, which share characteristics of both stimulatory Tfh cells and suppressive regulatory T (Treg) cells, restrain excessive GC responses. Tfh cell differentiation is a multistep process that involves continuous interaction with antigen‐presenting cells, co‐stimulatory signals, an appropriate cytokine milieu, and directed migration toward distinct microanatomical structures. These processes are under the control of several intrinsic and extrinsic regulatory layers that further undergo fine‐tuning by post‐transcriptional mechanisms. MicroRNAs (miRNAs) are small, non‐coding RNAs that have been recognized as important post‐transcriptional regulators. miRNAs are particularly critical for Tfh cell generation, as the differentiation of these cells is completely blocked in the absence of mature miRNAs in vivo. Here, we discuss how miRNAs regulate various aspects of Tfh and Tfr cell differentiation and function and how miRNAs thus shape the identity of these cells.
Linking signaling and selection in the germinal center
Authors: Shlomchik Mark J. , Luo Wei , Weisel Florian 
Published: March 2019

SummaryGerminal centers (GC) are sites of rapid B‐cell proliferation in response to certain types of immunization. They arise in about 1 week and can persist for several months. In GCs, B cells differentiate in a unique way and begin to undergo somatic mutation of the Ig V regions at a high rate. GC B cells (GCBC) thus undergo clonal diversification that can affect the affinity of the newly mutant B‐cell receptor (BCR) for its driving antigen. Through processes that are still poorly understood, GCBC with higher affinity are selectively expanded while those with mutations that inactivate the BCR are lost. In addition, at various times during the extended GC reaction, some GCBC undergo differentiation into either long‐lived memory B cells (MBC) or plasma cells. The cellular and molecular signals that govern these fate decisions are not well‐understood, but are an active area of research in multiple laboratories. In this review, we cover both the history of this field and focus on recent work that has helped to elucidate the signals and molecules, such as key transcription factors, that coordinate both positive selection as well as differentiation of GCBC.
Democracy as Uninformed Non‐Consent
Authors: Brennan Jason 
Published: March 2019

AbstractCarol Gould argues that democratic institutions can serve as mechanisms of informed consent or could at least facilitate creating regulations and other structures which facilitate informed consent in bioethics, medicine, and elsewhere. I am sceptical. I argue that democracies cannot serve as vehicles of consent, let alone informed consent. Further, the problems of democratic ignorance and irrationality created significant barriers to democratic deliberation helping to produce better regulations or conditions for informed consent. Democracy is not a good surrogate for consent.
Reaction norm analysis of pig growth using environmental descriptors based on alternative traits
Authors: Guy Sarita Zhe Ying , Li Li , Thomson Peter Campbell , Hermesch Susanne 
Published: March 2019

AbstractContemporary group (CG) estimates of different phenotypes have not been widely explored for pigs. The objective of this study was to extend the traits used to derive environmental descriptors of the growing pig, to include CG estimates of early growth between birth and start of feed intake test (EADG), growth during feed intake test (TADG), lifetime growth (ADG), daily feed intake (DFI), backfat (BF) and muscle depth (MD). Pedigree and performance records (n = 7,746) from a commercial Australian piggery were used to derive environmental descriptors based on CG estimates of these six traits. The CG estimates of growth traits described different aspects of the environment from the CG estimates of carcass traits (r < 0.10). These definitions of the environment then were used in reaction norm analysis of growth, to evaluate sire‐by‐environment interaction (Sire × E) for growth. The most appropriate reaction norm model to evaluate Sire × E for growth was dependent on the environmental descriptor used. If the trait used to derive an environmental descriptor was distinctly different from growth (e.g., BF and MD), CG as an additional random effect was required in the model. If not included, inflated common litter effect and sire intercept variance suggest there was unaccounted environmental variability. There was no significant Sire × E using any of the definitions of the environment, with estimated variance in sire slopes largest when environments were defined by BF ( = 97 ± 83 (g/day)2), followed by environments defined by DFI ( = 39 ± 101 (g/day)2). While there appears to be differences in ability to detect Sire × E, improved data structure is required to better assess these environmental descriptors based on alternative traits. The ideal trait, or combination of traits, used to derive environmental descriptors may be unique for individual herds. Therefore, multiple phenotypes should be further explored for the evaluation of Sire × E for growth in the pig.
Challenges and opportunities to livestock breeding programmes in India
Authors: Gowane Gopal R. , Kumar Arun , Nimbkar Chanda 
Published: March 2019

AbstractAnimal breeding in India has a long and chequered history. High pressure on agricultural land and increasing human population opened a new opportunity for the livestock and poultry sector as a promising food industry. Productivity of livestock in India is low due to less coverage of livestock under structured breeding programmes, inadequate nutrition and its entanglement with several socio‐economic issues. A bottom‐up approach to breeding policy formulation addressing local needs is required with assured flow of investments. Cattle slaughter is banned in India; hence, a legal policy to curb widespread indiscriminate mating is required which may incur substantial financial and infrastructural burdens for castration of stray males and strengthening of cow rehabilitation centres. Genetic evaluation of indigenous cattle with progeny testing (PT) requires substantial financial support, without affecting the already existing PT for exotic cattle breeds used in the local cross‐breeding programmes and PT of new genotypes obtained from crosses of exotic and local breeds of cattle and for purebred buffaloes. Small ruminants need special attention due to their socio‐economic importance in rural and often highly disadvantaged communities and because they are the second most important meat‐producing species after poultry. Genetic improvement of small ruminants should be accompanied by attention to shrinking grazing resources which would require strong political will together with financial support. The outreach of breeding programmes for small ruminants is currently limited; there is also a lack of linkage between the market and producers that discourages farmers from adopting clear breeding objectives like improvement in growth rate, as animals are seldom sold on weight basis. Apart from government agencies, involvement of private sector, non‐government organizations, local co‐operatives, self‐help groups and self‐sustainable community‐based breeding programmes can strengthen market linkages. Strengthening of the existing infrastructure along with technical input and skilled manpower is essential for achieving the breeding objectives.
CTCF regulates the FoxO signaling pathway to affect the progression of prostate cancer
Authors: Shan Zhengfei , Li Yongwei , Yu Shengqiang , Wu Jitao , Zhang Chengjun , Ma Yue , Zhuang Guimin , Wang Jiantao , Gao Zhenli , Liu Dongfu 
Published: March 2019

AbstractThe present research focuses on the influence of CCCTC‐binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP‐seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT‐qPCR and Western blot. Inhibition of CTCF could lead to the up‐regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down‐regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.
Ectopic expression of miR‐944 impairs colorectal cancer cell proliferation and invasion by targeting GATA binding protein 6
Authors: Tang Jing‐Tong , Zhao Jinbo , Sheng Weiwei , Zhou Jian‐Ping , Dong Qi , Dong Ming 
Published: March 2019

AbstractmiR‐944 is a microRNA that has been reported to play different important roles in the progression of cancer. Colorectal cancer (CRC) is a common cancer worldwide. A recent study has confirmed that miR‐944 plays a tumour suppressive role in CRC. However, biological functions and the mechanism of miR‐944 in CRC are poorly understood. Real‐time reverse transcription polymerase chain reaction of 100 CRC tissues showed that miR‐944 expression is frequently downregulated and is negatively associated with the T is the primary tumor, N is the lymph node, and M is the distant metastasis (TNM) stage (P = 0.009), depth of invasion (P = 0.001), and lymph node status (P = 0.002). Overexpression of mir‐944 significantly impaired the functions of proliferation, migration and invasion in CRC cells, while these functions increased in knockdown experiments. GATA binding protein 6 (GATA6) knockdown can reverse the CRC cells functions induced by miR‐944 inhibitor. Mechanistically, a Dual‐Luciferase Reporter Assay showed that miR‐944 is structurally combined with GATA6 and interacts with downstream proteins (CRT and p‐AKT) in CRC cells. In conclusion, these findings indicated that miR‐944 may be a tumour suppressor and could likely be used as a prognostic predictor and novel therapeutic target for CRC.
Laser treatment of hyperpigmented lesions: position statement of the European Society of Laser in Dermatology
Authors: Passeron T. , Genedy R. , Salah L. , Fusade T. , Kositratna G. , Laubach H.‐J. , Marini L. , Badawi A. 
Published: March 2019

AbstractBackgroundLasers and intense pulsed light sources (IPLS) are proposed for the treatment of many pigmentary disorders. They are sometimes considered as magic tools able to remove any type of lesions. Although being the best option for several hyperpigmented lesions, they can also worsen some conditions and have potential side‐effects.ObjectiveThe aim of this review was to give evidence‐based recommendations for the use of lasers and IPLS in the treatment of hyperpigmented lesions.MethodsThese recommendations were produced for the European Society of Laser Dermatology by a consensus panel made up of experts in the field of pigment laser surgery. Recommendations on the use of lasers and light treatments were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts' opinion.ResultsLasers and IPLS are very effective for treating many hyperpigmented lesions such as lentigos, dermal hypermelanocytosis or heavy metal depositions. In the other hand, they have to be considered with great caution for other disorders, such as café au lait macules, melasma or postinflammatory hyperpigmentation. After making the correct diagnosis, if lasers or IPLS are indicated, the optimal wavelengths and parameters will be chosen taking into account the skin phototype, origin and depth of the target pigments.ConclusionAlthough potentially very effective, lasers and IPLS cannot be proposed for all types of hyperpigmented lesions. In all cases, precise recognition of the disorder is mandatory for choosing between these devices and other therapeutic approaches.
Innate immunity, inflammation and tumour progression: double‐edged swords
Authors: Mantovani A. , Ponzetta A. , Inforzato A. , Jaillon S. 
Published: March 2019

AbstractComponents of the cellular and the humoral arm of the immune system are essential elements of the tumour microenvironment (TME). The TME includes tumour‐associated macrophages which have served as a paradigm for the cancer‐promoting inflammation. Cytokines, IL‐1 in particular, and complement have emerged as important players in tumour promotion. On the other hand, myeloid cells, innate lymphoid cells and complement have the potential, if unleashed, to mediate anticancer resistance. Targeting checkpoints restraining innate immunity, macrophages and natural killer (NK) cells in particular holds promise as a therapeutic strategy.
Values of Economists Matter in the Art and Science of Economics
Authors: van Dalen Hendrik P. 
Published: March 2019

SummaryWhat role do personal values play in the practice of economists? By means of a survey among economists working inside and outside academia in the Netherlands, we present novel insights on their personal values, how these differ from the average citizen, and how values impact their economic views and their methodological choices. Three overarching values summarize the value structure of economists: achievement, serving the public interest, and conformity to rules. Subsequent tests are performed to see whether these values affect (1) their opinion on economic propositions and (2) their attitudes towards methodological principles in economics. For the majority of economic propositions, personal values matter. Especially the value of serving the public interest has a strong effect on their economic view. Furthermore, it seems that economists who value achievement are the ones who are more likely to embrace mainstream methodological principles: thinking predominantly in terms of efficiency, rationality, and competition, believing that economic knowledge is objective and transparently produced and in agreement with Milton Friedman's view on positive economics. Female economists are at some notable points less convinced of market solutions and have more trust in the government in serving the public interest.
A non‐coding RNA from the intercellular adhesion (ica) locus of Staphylococcus epidermidis controls polysaccharide intercellular adhesion (PIA)‐mediated biofilm formation
Authors: Lerch Maike F. , Schoenfelder Sonja M.K. , Marincola Gabriella , Wencker Freya D.R. , Eckart Martin , Förstner Konrad U. , Sharma Cynthia M. , Thormann Kai M. , Kucklick Martin , Engelmann Susanne , Ziebuhr Wilma 
Published: March 2019

SummaryPolysaccharide intercellular adhesin (PIA)‐associated biofilm formation is mediated by the intercellular adhesin (ica) locus and represents a major pathomechanism of Staphylococcus epidermidis. Here, we report on a novel long non‐coding (nc)RNA, named IcaZ, which is approximately 400 nucleotides in size. icaZ is located downstream of the ica repressor gene icaR and partially overlaps with the icaR 3ʹ UTR. icaZ exclusively exists in ica‐positive S. epidermidis, but not in S. aureus or other staphylococci. Inactivation of the gene completely abolishes PIA production. IcaZ is transcribed as a primary transcript from its own promoter during early‐ and mid‐exponential growth and its transcription is induced by low temperature, ethanol and salt stress. IcaZ targets the icaR 5ʹ UTR and hampers icaR mRNA translation, which alleviates repression of icaADBC operon transcription and results in PIA production. Interestingly, other than in S. aureus, posttranscriptional control of icaR mRNA in S. epidermidis does not involve icaR mRNA 5ʹ/3ʹ UTR base pairing. This suggests major structural and functional differences in icaADBC operon regulation between the two species that also involve the recruitment of ncRNAs. Together, the IcaZ ncRNA represents an unprecedented novel species‐specific player involved in the control of PIA production in NBSP S. epidermidis.
Technical approaches to select high‐performance instant skin smoothing formulations: Correlation of in vitro and in vivo assessment methods
Authors: Maidhof Robert , Knapp Elizabeth , Liebel Frank , Fair Michael , Rubinson Emily H. 
Published: March 2019

AbstractBackgroundContractile films that smooth the surface of skin upon drying are popular among consumers due to their “instant” effect and perceivable smoothing benefits. The objective of our study was to correlate an in vitro measurement of contractile force with in vivo smoothing performance, thereby enabling rapid screening of film‐forming technologies for impactful cosmetic results.MethodsWe introduce and characterize an in vitro method to measure drying stress of film‐containing formulations. This method is used to measure the drying stresses of seven different cosmetic film formulations. We then evaluate these formulas in a blinded clinical study, measuring their effect on under‐eye and Crow's Feet area smoothing through bioinstrumentation (3D PRIMOS imaging) and blinded expert grading of images.ResultsThe in vitro drying stress measurement was found to be repeatable and sensitive enough to detect differences between formulations with typical amounts of film‐forming agents. Significant correlation was found between the in vitro drying stress measurements and under‐eye smoothing measured by 3D imaging (R2 = 0.71). Expert grading confirmed that film formulas deliver perceivable smoothing in the under‐eye and Crow's Feet regions 15 minutes after application.ConclusionThe in vitro method described here can be used to predict the efficacy of formulations that deliver smoothing benefits to consumers. For consumer use, the esthetic properties of a formula should be balanced with film performance, guided by this model which predicts skin smoothing efficacy.
Residential Segregation in the Amsterdam Metropolitan Region: A Longitudinal Analysis Using Scalable Individualised Neighbourhoods
Authors: Sleutjes Bart , Ooijevaar Jeroen , de Valk Helga A.G. 
Published: March 2019

AbstractThis paper studies residential segregation in the Amsterdam Metropolitan Area and makes three contributions to the recent debates on segregation. First, both ethnic and socio‐economic segregation are studied by comparing isolation index scores for both individual indicators and their interactions. Second, neighbourhoods are defined as scalable individualised units, which allows for comparisons across spatial scales. Third, the paper adopts a longitudinal approach by covering three different time points, which enables us to get a grip on segregation trends. The results indicate that there are notable differences in segregation levels and trends between the applied segregation indicators. Ethnic segregation remained largely stable over the 2003–14 period, whereas the indicators of socio‐economic segregation have slightly changed, but all in different directions. Only for tertiary education segregation has increased over the entire period. The Dutch welfare system, the well‐dispersed and socially‐mixed social housing sector and gentrification help to explain these developments.
Surface Structures of Group BStreptococcusImportant in Human Immunity
Authors: Paoletti Lawrence C. , Kasper Dennis L. 
Published: March 2019

ABSTRACTThe surface of the Gram-positive opportunistic pathogen Streptococcus agalactiae, or group B Streptococcus (GBS), harbors several carbohydrate and protein antigens with the potential to be effective vaccines. Capsular polysaccharides of all clinically-relevant GBS serotypes coupled to immunogenic proteins of both GBS and non-GBS origin have undergone extensive testing in animals that led to advanced clinical trials in healthy adult women. In addition, GBS proteins either alone or in combination have been tested in animals; a fusion protein construct has recently advanced to human clinical studies. Given our current understanding of the antigenicity and immunogenicity of the wide array of GBS surface antigens, formulations now exist for the generation of viable vaccines against diseases caused by GBS.