The barocaloric effect: A Spin-off of the Discovery of High-Temperature Superconductivity

Some key results obtained in joint research projects with Alex M\"uller are summarized, concentrating on the invention of the barocaloric effect and its application for cooling as well as on important findings in the field of high-temperature superconductivity resulting from neutron scattering experiments.Comment: 26 pages, 9 figure

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry

Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia. However, due to the difficulties in handling human postmortem brains, particularly the large size and complex structures of the human brain, there is little agreement regarding the qualitative and quantitative abnormalities of phospholipids in brains from patients with schizophrenia, particularly if corresponding brain regions are not used. In this study, to overcome these problems, we employed matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS), enabling direct microregion analysis of phospholipids in the postmortem brain of a patient with schizophrenia via brain sections prepared on glass slides. With integration of traditional histochemical examination, we could analyze regions of interest in the brain at the micrometric level. We found abnormal phospholipid distributions within internal brain structures, namely, the frontal cortex and occipital cortex. IMS revealed abnormal distributions of phosphatidylcholine molecular species particularly in the cortical layer of frontal cortex region. In addition, the combined use of liquid chromatography/electrospray ionization tandem mass spectrometry strengthened the capability for identification of numerous lipid molecular species. Our results are expected to further elucidate various metabolic processes in the neural system

Advances in Pediatric Neurovirology

Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease

Development of Cysteine-Free Fluorescent Proteins for the Oxidative Environment

Molecular imaging employing fluorescent proteins has been widely used to highlight specific reactions or processes in various fields of the life sciences. Despite extensive improvements of the fluorescent tag, this technology is still limited in the study of molecular events in the extracellular milieu. This is partly due to the presence of cysteine in the fluorescent proteins. These proteins almost cotranslationally form disulfide bonded oligomers when expressed in the endoplasmic reticulum (ER). Although single molecule photobleaching analysis showed that these oligomers were not fluorescent, the fluorescent monomer form often showed aberrant behavior in folding and motion, particularly when fused to cysteine-containing cargo. Therefore we investigated whether it was possible to eliminate the cysteine without losing the brightness. By site-saturated mutagenesis, we found that the cysteine residues in fluorescent proteins could be replaced with specific alternatives while still retaining their brightness. cf(cysteine-free)SGFP2 showed significantly reduced restriction of free diffusion in the ER and marked improvement of maturation when fused to the prion protein. We further applied this approach to TagRFP family proteins and found a set of mutations that obtains the same level of brightness as the cysteine-containing proteins. The approach used in this study to generate new cysteine-free fluorescent tags should expand the application of molecular imaging to the extracellular milieu and facilitate its usage in medicine and biotechnology

Interleukin-10 inhibits osteoclastogenesis by reducing NFATc1 expression and preventing its translocation to the nucleus

BACKGROUND: IL-10 has a potent inhibitory effect on osteoclastogenesis. In vitro and in vivo studies confirm the importance of this cytokine in bone metabolism, for instance IL-10-deficient mice develop the hallmarks of osteoporosis. Although it is known that IL-10 directly inhibits osteoclastogenesis at an early stage, preventing differentiation of osteoclast progenitors to preosteoclasts, the precise mechanism of its action is not yet clear. Several major pathways regulate osteoclastogenesis, with key signalling genes such as p38, TRAF6, NF-κB and NFATc1 well established as playing vital roles. We have looked at gene expression in eleven of these genes using real-time quantitative PCR on RNA extracted from RANKL-treated RAW264.7 monocytes. RESULTS: There was no downregulation by IL-10 of DAP12, FcγRIIB, c-jun, RANK, TRAF6, p38, NF-κB, Gab2, Pim-1, or c-Fos at the mRNA level. However, we found that IL-10 significantly reduces RANKL-induced NFATc1 expression. NFATc1 is transcribed from two alternative promoters in Mus musculus and, interestingly, only the variant transcribed from promoter P1 and beginning with exon 1 was downregulated by IL-10 (isoform 1). In addition, immunofluorescence studies showed that IL-10 reduces NFATc1 levels in RANKL-treated precursors and suppresses nuclear translocation. The inhibitory effect of IL-10 on tartrate-resistant acid phosphatase-positive cell number and NFATc1 mRNA expression was reversed by the protein kinase C agonist phorbol myristate acetate, providing evidence that interleukin-10 disrupts NFATc1 activity through its effect on Ca(2+ )mobilisation. CONCLUSION: IL-10 acts directly on mononuclear precursors to inhibit NFATc1 expression and nuclear translocation, and we provide evidence that the mechanism may involve disruption of Ca(2+ )mobilisation. We detected downregulation only of the NFATc1 isoform 1 transcribed from promoter P1. This is the first report indicating that one of the ways in which IL-10 directly inhibits osteoclastogenesis is by suppressing NFATc1 activity

Low-dose aspirin does not improve ovarian stimulation, endometrial response, or pregnancy rates for in vitro fertilization

BACKGROUND: The purpose of this study is to determine if low-dose aspirin improved ovarian stimulation, endometrial response, or IVF pregnancy rates in our program. METHODS: Retrospective analysis of 316 consecutive IVF cycles from 1995 through 2001. Aspirin 80 mg daily was initiated at the start of luteal leuprolide in 72 cycles. The 244 controls received no aspirin during treatment. RESULTS: The live birth rate in aspirin users was 29%, slightly lower compared to 41% in the no aspirin control group (p = 0.07). Implantation rates were 21% with aspirin and 30% in the control population (p = 0.01). There was no difference in the maximal endometrial thickness between aspirin and non-aspirin groups. The two groups were similar regarding age, gonadotropin ampules, embryos, number of embryos transferred, prior parity, diagnosis, use of intracytoplasmic sperm injection, and stimulation protocol. CONCLUSION: Low-dose aspirin was not beneficial to IVF patients in our program. Aspirin does not enhance endometrial thickness, augment the ovarian response, or improve pregnancy rates

Molecular therapy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further