Potential For Basic Research Research Articles

Optical Molecular Probes for Imaging and Early Diagnosis of Acute Kidney Injury.

The kidneys play an irreplaceable role in metabolism and excretion. However, Acute Kidney Injury (AKI) often occurs due to high local concentrations of drugs, inflammation, and trauma. Activated optical probes with excellent detection performance can effectively identify biomarkers in the initial stage of AKI and play an important role in evaluating AKI and preventing the development of diseases. This article summarizes representative design strategies for molecular probes and special diagnostic applications. These molecular probes show great potential in basic research and clinical diagnosis, enabling enhanced images of tissue structure and biomarkers, as well as early diagnosis of AKI. In addition, the difficulties and challenges that optical probes may face in the development and application of AKI are also discussed in this article.

MRNA epitranscriptomics.

Epitranscriptomics refers to chemical changes in RNAs and includes numerous chemical types with varying stoichiometry and functions. RNA modifications are highly diverse in chemistry and respond in cell-type- and cell-state-dependent manners that enable and facilitate the execution of a wide array of biological functions. This includes roles in the regulation of transcription, translation, chromatin maintenance, immune response, and many other processes. This special issue presents the past, present, and future of epitranscriptomics research with a focus on mRNA. It includes perspectives from experts in the field, with the goal of encouraging discussions and debates that will further advance this area of research and enable it to realize its full potential in basic research and applications to human health and disease.

Membrane-Active Peptides and Their Potential Biomedical Application.

Membrane-active peptides (MAPs) possess unique properties that make them valuable tools for studying membrane structure and function and promising candidates for therapeutic applications. This review paper provides an overview of the fundamental aspects of MAPs, focusing on their membrane interaction mechanisms and potential applications. MAPs exhibit various structural features, including amphipathic structures and specific amino acid residues, enabling selective interaction with multiple membranes. Their mechanisms of action involve disrupting lipid bilayers through different pathways, depending on peptide properties and membrane composition. The therapeutic potential of MAPs is significant. They have demonstrated antimicrobial activity against bacteria and fungi, making them promising alternatives to conventional antibiotics. MAPs can selectively target cancer cells and induce apoptosis, opening new avenues in cancer therapeutics. Additionally, MAPs serve as drug delivery vectors, facilitating the transport of therapeutic cargoes across cell membranes. They represent a fascinating class of biomolecules with significant potential in basic research and clinical applications. Understanding their mechanisms of action and designing peptides with enhanced selectivity and efficacy will further expand their utility in diverse fields. Exploring MAPs holds promise for developing novel therapeutic strategies against infections, cancer, and drug delivery challenges.

Preparation and characterization of a high-affinity monoclonal antibody against nerve growth factor

Nerve growth factor (NGF) is produced and released in injured tissues or chronic pain tissues caused by other diseases. Studies have shown that monoclonal antibodies targeting NGF have a good efficacy in the treatment of osteoarthritis (OA), low back pain and chronic pain, which may be a promising therapy. In this study, DNA sequences of NGF-his and NGF-hFc were synthesized using eukaryotic expression system and subcloned into pTT5 expression vector. After that, NGF proteins were expressed by transient expression in HEK293E cells. We immunized mice with NGF-hFc protein and fused mouse spleen cells to prepare hybridomas. NGF-His protein was used to screen out the hybridoma supernatant that could directly bind to NGF. Antibodies were purified from hybridioma supernatant. Futhermore, via surface plasmon resonance (SPR) screening, six anti-NGF mAbs were screened to block the binding of NGF and TrkA receptor in the treatment of chronic pain. Among them, 58F10G10H showed high affinity (KD = 1.03 × 10−9 M) and even better than that of positive control antibody Tanezumab (KD = 1.53 × 10−9 M). Moreover, the specific reactivity of 58F10G10H was demonstrated by TF-1 cell proliferation activity experiments, competitive binding Enzyme-linked immunosorbent assay (ELISA) and the arthritis animal models in mice, respectively. In conclusion, in this study, a method for the preparation of high-yield NGF-HFC and NGF-His proteins was designed, and a high-affinity monoclonal antibody against NGF with potential for basic research and clinical application was prepared.

Perfecting Targeting in CRISPR.

CRISPR-based genome editing holds promise for genome engineering and other applications in diverse organisms. Defining and improving the genome-wide and transcriptome-wide specificities of these editing tools are essential for realizing their full potential in basic research and biomedical therapeutics. This review provides an overview of CRISPR-based DNA- and RNA-editing technologies, methods to quantify their specificities, and key solutions to reduce off-target effects for research and improve therapeutic applications.

Reprogramming of Fibroblasts to Neural Stem Cells by a Chemical Cocktail.

Chemically induced cell fate conversion, including reprogramming to pluripotent stem cells and direct reprogramming to somatic cells, has been proved to be an alternative strategy with many advantages, in comparison with conventional transcription factors- or microRNAs-enabled cell reprogramming. Many functional and desirable cells have been generated via the chemically induced reprogramming. Neural stem cells (NSCs) hold great potential in basic research and clinical application. Here, we describe a detailed protocol for converting mouse fibroblasts into NSCs by a cocktail of chemical compounds.

Scanning tunneling microscopy study on two-dimensional topological insulators

Topological state is a rapidly emerging branch of condensed matter physics in recent years, among which two-dimensional topological insulators (2D TIs) have attracted wide attentions due to their great potential in basic research and applications. The 2D TI has insulating bulk state and conductive edge state. Its edge state is protected by time inversion symmetry and will not be backscattered by weak disordered impurities on the boundaries, thus forming a dissipationless edge conductive channel. Compared with 3D TIs, the edge state of 2D TIs can only propagate in two directions, meaning stronger anti-interference with robustness, thus is of great significance for the development of advanced integrated circuits with low energy consumption. Among many experimental methods for studying two-dimensional materials, scanning tunneling microscopy is a surface-sensitive tool with high atomic and energy resolution to locally detect the electronic structure of the material surface. By detecting the edge state of 2D materials in real space, it is particularly suitable for characterizing their topological properties. This paper traces the research progress of 2D TIs, and illustrates their spectroscopic evidences to resolve the nontrivial properties of the one-dimensional edge states. Combined with theoretical calculations, the topological edge states are verified to reside within the bulk energy gap, as well as being localized in the vicinity of step boundaries with a specific spatial distribution in real space. Finally, we discuss the tunability and manipulations of 2D topological materials through structural and external fields, which show promising prospects for applications in future spintronics and energy-saving devices.

Decoding Subjective Intensity of Nociceptive Pain from Pre-stimulus and Post-stimulus Brain Activities.

Pain is a highly subjective experience. Self-report is the gold standard for pain assessment in clinical practice, but it may not be available or reliable in some populations. Neuroimaging data, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have the potential to be used to provide physiology-based and quantitative nociceptive pain assessment tools that complements self-report. However, existing neuroimaging-based nociceptive pain assessments only rely on the information in pain-evoked brain activities, but neglect the fact that the perceived intensity of pain is also encoded by ongoing brain activities prior to painful stimulation. Here, we proposed to use machine learning algorithms to decode pain intensity from both pre-stimulus ongoing and post-stimulus evoked brain activities. Neural features that were correlated with intensity of laser-evoked nociceptive pain were extracted from high-dimensional pre- and post-stimulus EEG and fMRI activities using partial least-squares regression (PLSR). Further, we used support vector machine (SVM) to predict the intensity of pain from pain-related time-frequency EEG patterns and BOLD-fMRI patterns. Results showed that combining predictive information in pre- and post-stimulus brain activities can achieve significantly better performance in classifying high-pain and low-pain and in predicting the rating of perceived pain than only using post-stimulus brain activities. Therefore, the proposed pain prediction method holds great potential in basic research and clinical applications.

Increasing the public health potential of basic research and the scientist satisfaction. An international survey of bioscientists.

Basic scientific research generates knowledge that has intrinsic value which is independent of future applications. Basic research may also lead to practical benefits, such as a new drug or diagnostic method. Building on our previous study of basic biomedical and biological researchers at Harvard, we present findings from a new survey of similar scientists from three countries. This survey asked about the scientists' motivations, goals and perspectives along with their attitudes concerning policies designed to increase both the practical (i.e. public health) benefits of basic research as well as their own personal satisfaction. Close to 900 basic investigators responded to the survey; results corroborate the main findings from the previous survey of Harvard scientists. In addition, we find that most bioscientists disfavor present policies that require a discussion of the public health potential of their proposals in grants but generally favor softer policies aimed at increasing the quality of work and the potential practical benefits of basic research. In particular, bioscientists are generally supportive of those policies entailing the organization of more meetings between scientists and the general public, the organization of more academic discussion about the role of scientists in the society, and the implementation of a "basic bibliography" for each new approved drug.

EMMPRIN in gynecologic cancers: pathologic and therapeutic aspects.

The highly glycosylated transmembrane protein extracellular matrix metalloproteinase inducer (EMMPRIN) is associated with several pathological conditions, including various types of cancers. In different gynecological malignancies, such as ovarian, cervical, and endometrial cancers, EMMPRIN plays significant roles in cell adhesion modulation, tumor growth, invasion, angiogenesis, and metastasis by inducing the production of various molecules, including matrix metalloproteinases and vascular endothelial growth factor. Because of its high level of expression, EMMPRIN can possibly be used as a diagnostic marker of gynecological cancers. Recent studies have showed that targeting EMMPRIN, especially by RNA interference (RNAi) technology, has promising therapeutic potential in basic research on gynecological cancer treatments, which make a platform for the future clinical success. This review study focused on the association of EMMPRIN in gynecological cancers in the perspectives of pathogenesis, diagnosis, and therapeutics.

Stem Cell Research.

Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective.

Imaging preclinical tumour models: improving translational power.

Recent developments and improvements of multimodal imaging methods for use in animal research have substantially strengthened the options of in vivo visualization of cancer-related processes over time. Moreover, technological developments in probe synthesis and labelling have resulted in imaging probes with the potential for basic research, as well as for translational and clinical applications. In addition, more sophisticated cancer models are available to address cancer-related research questions. This Review gives an overview of developments in these three fields, with a focus on imaging approaches in animal cancer models and how these can help the translation of new therapies into the clinic.

Where the rubber hits the road: the translational pulse of reproductive biology

As a journal, MHR is not unique in facing a future with many challenges relating to potential scientific misconduct, the publication of data, open versus restricted access, electronic versus paper publishing and more. We are continually trying to assess how people read journals and importantly the most effective ways to assist our audience in providing the information they require how and when they need it. MHR as part of the European Society of Human Reproduction and Embryology (ESHRE) stable and in collaboration with Oxford University Press (OUP) is facing such challenges from a position of enormous strength. The considerable resources and experience of OUP and ESHRE allow us to innovate and take calculated risks. The primary role of MHR is to solicit and publish high-quality papers that have the clear potential to make an important impact on our discipline. This is where MHR has and will continue to focus. Steve Hillier pioneered and continually drove this agenda with boundless enthusiasm, commitment, remarkable skill and a high degree of acumen. It is my task, along with the Associate Editors, to reinforce this momentum and maintain a forward trajectory. Using the New Research Horizon Reviews and a collection of papers around a common theme, MHR has been very successful in publishing key papers focussing on the scientific/clinical interface of reproductive medicine. An example is related to the potential power of the ‘omics’ revolution. Another is the packaging and the impact of damage to the paternal genome. Both special issues have been very well received and cited (in the range 4–16 cites per paper per citation year). Additionally, we have sought and published important primary data manuscripts. The editorial strategy for the next 3 years will be to continue to solicit papers, where there are clear mechanisms addressed and to heighten the focus on the basic science and the basic science/clinical interface—‘where the rubber hits the road’. There is a tremendous amount to do in this arena. One of the many fascinating aspects of reproductive medicine is the willingness and speed with which potential new developments are translated into the clinical practice. Sometimes, this has been too rapid, but it illustrates the great potential of basic research in the discipline to make an immediate impact. A very important challenge is to incorporate into our subject the skills and knowledge from related disciplines. An example is that of developmental biology. Sperm oocyte interaction and the resultant early embryo development involve breathtaking changes in the cells encompassing fundamental issues such as reprogramming and cell fate to name a few. Now, with the use, for example, of time lapse imaging and the accessibility of defined populations of human embryos, is the time to marry the areas of developmental biology and assisted conception. The focus should not just apply to animal biology. Plants hold key lessons to be learnt for example in the fertilization process. There is scope for bringing different disciplines together, e.g. ‘The sperm flagella—where physics and mathematics meet biology and engineering’. There could be tremendous potential benefits from bridging subjects, addressing common problems and putting these in the context of reproductive medicine. So, the editorial strategy is to try and encourage the above interactions by securing high-quality primary papers and developing a series of hard hitting themes. The Associate Editors have been charged with these tasks. Your fellow reproductive biologists should be beside themselves with excitement. If not, check they have a pulse!

Abstract 3023: Rapid methylation profiling of multiple genes at the same time using the methylation ligation-dependent macroarray (MLM)

Abstract Background: Aberrant methylation of multiple promoter CpG islands is a common event in human cancers. Methylation profile of cancer-related genes has extraordinary potential in basic research as well as translational medicine. The aim of this study was to replace the tedious and inefficient bisulfite-based methods with a simple technology which could permit a rapid and robust analysis of large numbers of genes in large numbers of tumor samples simultaneously. Materials and methods: Genomic DNA was first sonicated, then couples of primers for each specific gene promoter were annealed to this DNA. In a one-step reaction, the CfoI methylation-sensitive enzyme digested unmethylated DNA, whereas the Taq ligase joined primers annealed to the methylated sequence. Tagged ligation products were amplified by PCR and finally hybridized to a nylon membrane macroarray. Methylation Ligation-dependent Macroarray (MLM) allows the establishment of DNA methylation profiles on many samples (up to 21) and on many gene promoters (up to 45) in a simple reaction in 2-3 days. To validate this novel method, we used it to detect aberrant methylation in 14 cell lines and in DNA samples of 40 patients with a colorectal cancer. Results: In tumor cell lines, among the 42 genes investigated 23.7 (11-32) were found methylated whereas only 9 have been observed methylated in a normal fibroblast cell line (BJ). In normal colorectal tissues, about 12/40 gene promoters were found methylated; in colorectal cancers 16 to 36 genes were methylated. Methylated gene promoters identified in colorectal cancers were ADAMTS18 (78%), APC (28%), CDKN2A (20%), DKK2 (50%), GPx3 (48%), Mal (72%), MLH1 (30%), NELL1 (72%), SFRP4 (35%), SFRP5 (52%) and WRN (20%): Conclusion: The MLM is a fast, non expensive and reliable technology that profiles the DNA methylation status of >40 promoter CpG islands in various human samples. This technology can be used in research for rapid methylation profiling of numerous samples and for identification of new epigenetic biomarkers, but also in clinic for rapid cancer diagnosis, for predictive response to cancer therapy and for distinction between progressive and non-progressive diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3023. doi:10.1158/1538-7445.AM2011-3023

Goodbye Germany - and then? Initial Results of a Pilot Survey of Emigrants from Germany (Goodbye Germany - und dann? Erste Ergebnisse einer Pilotstudie zur Befragung von Auswanderern aus Deutschland)

In contrast to the vast body of data on immigration to Germany, there is almost no scientifically valid data available on emigration flows from Germany and the factors motivating people to emigrate. In particular, there is an almost total lack of data on the living conditions of emigrants after their arrival in their new home countries. It is thus unsurpising that the German emigration research is currently based mainly on aggregated emigration data from official statistical sources as well as on non-representative quantitative and qualitative studies of specific emigrant groups. This was the point of departure for the pilot project “Life outside Germany,” which attempted to follow Socio-Economic Panel Study (SOEP) participants who left Germany between 2002 and 2006, with the central aim of obtaining information about these individuals’ motivations for leaving and their living conditions in their new home countries. The project succeeded in locating 67 of the 288 former SOEP respondents who had been identified as emigrants. These individuals were sent the specially designed questionnaire by mail, and a total of 32 interviews were completed and returned. The present study starts by presenting the empirical findings from the pilot study. The main problem of the analysis lies less in the (controllable) selectivity of the respondents (32 of 288), and more the (still) extremely low case numbers, which do not allow scientifically sound conclusions to be drawn from the results. A further aim of this paper is therefore to provide an example of the basic research potential that lies in emigrant surveys, particularly in surveying SOEP respondents who have moved abroad. Linking information before and after the point of emigration creates new possibilities for empirical life-course research, which in turn - from an understanding of migration as a fundamentally open-ended process - open up new empirical perspectives for migration research.

Aplicaciones clínicas de la microscopía confocal de reflectancia en el manejo de los tumores cutáneos

Reflectance confocal microscopy is a noninvasive tool that allows skin cells and structure to be imaged in real time. The technique has been used to assess benign and malignant lesions and has shown great potential in basic research and clinical dermatology. As might be expected, it also has great potential in longitudinal clinical studies and in the evaluation of dynamic processes such as those that occur after exposure to UV radiation or during the tumor response to noninvasive therapy. This article briefly describes the fundamental aspects and basic principles of reflectance confocal microscopy and discusses its clinical applications essentially in the management of cutaneous tumors. We also consider the limitations of the technique associated with the optical properties of the skin, with instrumentation, and with interpretation of the images.

Clinical Applications of Reflectance Confocal Microscopy in the Management of Cutaneous Tumors

Reflectance confocal microscopy is a noninvasive tool that allows skin cells and structure to be imaged in real time. The technique has been used to assess benign and malignant lesions and has shown great potential in basic research and clinical dermatology. As might be expected, it also has great potential in longitudinal clinical studies and in the evaluation of dynamic processes such as those that occur after exposure to UV radiation or during the tumor response to noninvasive therapy. This article briefly describes the fundamental aspects and basic principles of reflectance confocal microscopy and discusses its clinical applications essentially in the management of cutaneous tumors. We also consider the limitations of the technique associated with the optical properties of the skin, with instrumentation, and with interpretation of the images.

Cross-linking properties of alginate gels determined by using advanced NMR imaging and Cu(2+) as contrast agent.

The entrapment of enzymes, drugs, cells or tissue fragments in alginates cross-linked with Ca(2+) or Ba(2+) has great potential in basic research, biotechnology and medicine. The swelling properties and, in turn, the mechanical stability are key factors in designing an optimally cross-linked hydrogel matrix. These parameters depend critically on the cross-linking process and seemingly minor modifications in manufacture have a large impact. Thus, sensitive and non-invasive tools are required to determine the spatial homogeneity and efficacy of the cross-linking process. Here, we show for alginate microcapsules (between 400 microm and 600 microm in diameter) that advanced (1)H NMR imaging, along with paramagnetic Cu(2+) as contrast agent, can be used to validate the cross-linking process. Two- and three-dimensional images and maps of the spin-lattice relaxation time T(1) of Ba(2+) cross-linked microcapsules exposed to external Cu(2+) yielded qualitative as well as quantitative information about the accumulation of Cu(2+) within and removal from microcapsules upon washing with Cu(2+) free saline solution. The use of Cu(2+) (having a slightly higher affinity constant to alginate than Ba(2+)) for gelling gave a complementary insight into the spatial homogeneity of the cross-linking process together with information about the mechanical stability of the microcapsules. The potential of this technique was demonstrated for alginates extracted from two different algal sources and cross-linked either externally by the conventional air-jet dropping method or internally by the "crystal gun" method.

The hybridoma revolution: an offshoot of basic research

In this narrative, I describe how my interest in the nature and origin of antibody diversity led me to tackle the problem by using somatic cell genetic techniques. The first hybridoma (an immortal antibody-secreting cell line derived by fusion of a short-lived lymphocyte and a myeloma cell line) was an offshoot of this approach. Although not intended for such purposes, it soon became obvious that this invention had widespread potential in basic research and industry. Indeed, the technique opened new inroads into the study of complex biological substances and became the method of choice to define new differentiation markers. Hybridomas also allowed us to dissect the immune response to a simple antigen and to demonstrate the critical role of somatic mutations in the generation of high affinity antibodies. Now, monoclonal antibodies can be derived and manipulated in vitro, leading to important new developments in therapeutic applications. BioEssays 1999;21:966–973. © 1999 John Wiley & Sons, Inc.

The hybridoma revolution: an offshoot of basic research.

In this narrative, I describe how my interest in the nature and origin of antibody diversity led me to tackle the problem by using somatic cell genetic techniques. The first hybridoma (an immortal antibody-secreting cell line derived by fusion of a short-lived lymphocyte and a myeloma cell line) was an offshoot of this approach. Although not intended for such purposes, it soon became obvious that this invention had widespread potential in basic research and industry. Indeed, the technique opened new inroads into the study of complex biological substances and became the method of choice to define new differentiation markers. Hybridomas also allowed us to dissect the immune response to a simple antigen and to demonstrate the critical role of somatic mutations in the generation of high affinity antibodies. Now, monoclonal antibodies can be derived and manipulated in vitro, leading to important new developments in therapeutic applications. BioEssays 1999;21:966-973.