Clinical characteristics of infections with cytomegalovirus in infants from personal observations]

An infection with cytomegaly virus had been diagnosed in 13 infants (including 4 neonates examined up to 2 weeks of life) out of 960 infants hospitalized within 3 years. Clinical examination most frequently revealed hepato- and splenomegaly, pneumonia and neurological disorders, and during a further stage of the clinical course psychomotoric retardation was noted in 7 out of 13 infants, and hearing loss in 5 out of 13 infants. A specific immunoglobulin G preparation (Cytotect) has been successfully used in all children, producing recovery or clinical improvement together with serologic improvement.     

Tau Overexpression Impacts a Neuroinflammation Gene Expression Network Perturbed in Alzheimer’s Disease

Filamentous inclusions of the microtubule-associated protein, tau, define a variety of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD). To better understand the role of tau-mediated effects on pathophysiology and global central nervous system function, we extensively characterized gene expression, pathology and behavior of the rTg4510 mouse model, which overexpresses a mutant form of human tau that causes Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We found that the most predominantly altered gene expression pathways in rTg4510 mice were in inflammatory processes. These results closely matched the causal immune function and microglial gene-regulatory network recently identified in AD. We identified additional gene expression changes by laser microdissecting specific regions of the hippocampus, which highlighted alterations in neuronal network activity. Expression of inflammatory genes and markers of neuronal activity changed as a function of age in rTg4510 mice and coincided with behavioral deficits. Inflammatory changes were tau-dependent, as they were reversed by suppression of the tau transgene. Our results suggest that the alterations in microglial phenotypes that appear to contribute to the pathogenesis of Alzheimer’s disease may be driven by tau dysfunction, in addition to the direct effects of beta-amyloid.     

Relationship between clinical data and gene expression in the HER2/ErbB2-dependent signaling pathway in patients with acute heart failure

Anticancer treatment with the human epidermal growth factor receptor (HER) 2 inhibitors can lead to significant myocardial dysfunction. The primary aim of the study was to estimate the possible association between gene expression in the ErbB signaling pathway and selected clinical event data in patients with acute heart failure. Twenty-four patients (19 males), aged 68.6?±?12.3 years, were diagnosed and treated due to acute heart failure. The globaltest method was used for the correlation between blood nuclear cells’ gene expression in the ErbB pathway (KEGG pathway id 04012) and important clinical data. Decreased expression of ErbB2/HER2 was found to be associated with the release of troponin and the need for inotropic support, whereas decreased neuregulin 1 (NRG1) expression was found to be associated with a decrease of ejection fraction below 40 % (globaltest p-value < 0.05). In summary, the ErbB signaling pathway and, especially, HER2/ErbB2 receptor expression are significantly associated with some of the recognized, clinically significant parameters of patients with acute heart failure. Evaluation of the molecular function of the HER2 receptor may be essential for the prognosis and targeted therapy of heart diseases.     

Investigation of the salt tolerance of new Polish bread and durum wheat cultivars

In some regions of the world, low annual precipitation necessitates irrigation of crop plants which usually leads to soil salinity. Due to climatic changes this effect is also expected in the countries of Central Europe, and so in Poland. The aim of the study was (1) to compare tolerance to salt stress of Polish Triticum aestivum cvs. ‘Bogatka’ and ‘Banderola’ with T. durum cv. ‘Komnata’ and breeding line 121, and (2) to indicate the physiological parameter/parameters most suitable for such comparison. The investigation was performed in two experiments. In the first one, the germination ability of caryopses and coleoptiles’ growth were estimated at 0–250 mM of NaCl. The second experiment was conducted on plants grown in a glasshouse in saline soil at 0–150 mM of NaCl for 6 weeks. Salt tolerance was evaluated on the basis of following parameters: chlorophyll fluorescence, net photosynthesis rate (P _N), transpiration rate (E), stomatal conductance (g _s), cell membrane permeability (EL), proline content, fresh weight (FW), dry weight (DW), and relative water content (RWC). Highest germination of caryopses of durum cultivars was recorded at all the salinity levels; however, their coleoptiles were shorter than coleoptiles of bread wheat cultivars. Analysis of chlorophyll fluorescence showed that applied salt doses did not disturb the light phase of photosynthesis in all cultivars under study. Plants of durum wheat showed the higher dissipation of energy excess at the level of the antenna chlorophyll (DIo/CSm) under salinity as compared to plants of bread wheat. Both ‘Komnata’ and line 121 showed stronger P _N reduction as an effect of salinity. A decline of P _N was closely connected with a decrease in g _s. The P _N correlated with a decrease in DW in all studied cultivars except ‘Bogatka’. Control plants of ‘Komnata’ and line 121 were characterized by higher EL and proline level than bread wheat cultivars. An increasing cell membrane permeability correlated with a decrease of RWC in ‘Banderola’ and ‘Komnata’. The content of proline under the increasing salinity correlated with changes of RWC in ‘Banderola’, ‘Komnata’ and line 121, which indicate protectoral role of proline against dehydration of tissue. Dry weight and RWC seem to be the parameters most useful in the salt-tolerance estimation of wheat plants. Taking into account the studied parameters ‘Banderola’ could be recognized as more salt tolerant, the degree of salinity tolerance of ‘Bogatka’ is the same as line 121, while ‘Komnata’ seems to be the most salt sensitive. The salt tolerance of T. aestivum and T. durum depends on the cultivar rather than the wheat species.     

Sporadic Alzheimer’s Disease Begins as Episodes of Brain Ischemia and Ischemically Dysregulated Alzheimer’s Disease Genes

The study of sporadic Alzheimer’s disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer’s disease, the basis of this entity is not yet clear. At present, the best-established and accepted “culprit” in Alzheimer’s disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may lead to pathological accumulation of amyloid in brain according to the “amyloid hypothesis.” We will critically review these observations and highlight inconsistencies between the predictions of the “amyloid hypothesis” and the published data. There is still controversy over the role of amyloid in the pathological process. A question arises whether amyloid is responsible for the neurodegeneration or if it accumulates because of the neurodegeneration. Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer’s disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia. Nowadays, a handful of researchers share a newly emerged view that the ischemic episodes of brain best describe the pathogenic cascade, which eventually leads to neuronal loss, especially in hippocampus, with amyloid accumulation, tau protein pathology and irreversible dementia of Alzheimer type. The most persuasive evidences come from investigations of ischemically damaged brains of patients and from experimental ischemic brain studies that mimic Alzheimer-type dementia. This review attempts to depict what we know and do not know about the triggering factor of the Alzheimer’s disease, focusing on the possibility that the initial pathological trigger involves ischemic episodes and ischemia-induced gene dysregulation. The resulting brain ischemia dysregulates additionally expression of amyloid precursor protein and amyloid-processing enzyme genes that, in addition, ultimately compromise brain functions, leading over time to the complex alterations that characterize advanced sporadic Alzheimer’s disease. The identification of the genes involved in Alzheimer’s disease induced by ischemia will enable to further define the events leading to sporadic Alzheimer’s disease-related abnormalities. Additionally, knowledge gained from the above investigations should facilitate the elaboration of the effective treatment and/or prevention of Alzheimer’s disease.     

Bioenergetic Constraints on Primate Abundance

Explaining variation in primate population densities is central to understanding primate ecology, evolution, and conservation. Yet no researchers to date have successfully explained variation in primate population density across dietary class and phylogeny. Most previous work has focused on measures of food availability, as access to food energy likely constrains the number of individuals supported in a given area. However, energy output may provide a measure of energy constraints on population density that does not require detailed data on food availability for a given taxon. Across mammals, many studies have shown that population densities generally scale with body mass^−0.75. Because individual energy expenditures scale with body mass^0.75, population energy use (the product of population density and individual energy use) does not change with body mass, which suggests the existence of energy constraints on population density across body sizes, i.e., taxa are limited to a given amount of energy use, constraining larger taxa to lower densities. We examined population energy use and individual energy expenditure in primates and tested this energy equivalence across body mass. We also used a residual analysis to remove the effects of body mass on primate population densities and energy expenditures using basal metabolic rates (BMR; kcal/d) as a proxy for total daily energy expenditure. After taking into account phylogeny, population energy use did not significantly correlate with body mass. Larger primates, which use more energy per day, live at lower population densities than smaller primates. In addition, we found a significant negative correlation between residuals of BMR from body mass and residuals of population density from body mass after taking phylogeny into account. Thus, energy costs constrain population density across a diverse sample of primates at a given body mass, and primate species that have relatively low BMRs exist at relatively high densities. A better understanding of the determinants of primate energy costs across geography and phylogeny will ultimately help us explain and predict primate population densities.     

Traditional Chinese medicine herbs - are they safe for psoriatic patients?

Although traditional Chinese medicine (TCM) relies on remedies of natural origin, its use is not always safe as it can have not only beneficial but also deleterious effects. Psoriatic patients, disappointed by conventional treatment and unaware of the potential side effects of TCM preparations, are increasingly reaching for non-traditional therapeutic methods. This review presents brief characteristics of selected Chinese herbs self-prescribed by psoriatic patients. It is important that dermatologists should be able to recognize any potential hazards connected with current or previous taking of these herbs by their patients.     

Analysis of copy number variants in the cattle genome

Copy number variation (CNV) is likely to be an important component of heritable variation in livestock. To characterise CNVs in cattle, we performed a genome wide survey to determine the number, location and gene content of these genomic features. A tiling oligonucleotide array with ~385,000 probes was used for comparative genomic hybridisation of both taurine and zebu cattle. Using a conservative set of calling criteria, a total of 51 CNV were detected that collectively spanned approximately half of one percent of the bovine genome. The size of the average CNV within each animal ranged from 213 kb up to 335 kb. Half of the CNV were detected in a single animal only, whilst the remainder was independently identified in multiple individuals. Analysis was performed to determine the gene content for each CNV region. This revealed that the majority of CNV (82%) spanned at least one gene, with a number of CNV containing genes which are known to control aspects of phenotypic variation in cattle. Whilst additional studies are required to determine the impact of individual CNV, this study confirmed them as an important class of genomic variation in cattle.     

Syntheses of novel myxopyronin B analogs as potential inhibitors of bacterial RNA polymerase

Based upon observations from our initial findings, additional myxopyronin B analogs have been prepared and tested for in vitro inhibitory activity against DNA-dependent RNA polymerase and antibacterial activity against Escherichia coli and Staphylococcus aureus.     

The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key events in the development of glioma, acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (ICC), and angioimmunoblastic T-cell lymphoma. They also cause D-2-hydroxyglutaric aciduria and Ollier and Maffucci syndromes. IDH1/2 mutations are associated with prolonged survival in glioma and in ICC, but not in AML. The reason for this is unknown. In their wild-type forms, IDH1 and IDH2 convert isocitrate and NADP⁺ to α-ketoglutarate (αKG) and NADPH. Missense mutations in the active sites of these enzymes induce a neo-enzymatic reaction wherein NADPH reduces αKG to D-2-hydroxyglutarate (D-2HG). The resulting D-2HG accumulation leads to hypoxia-inducible factor 1α degradation, and changes in epigenetics and extracellular matrix homeostasis. Such mutations also imply less NADPH production capacity. Each of these effects could play a role in cancer formation. Here, we provide an overview of the literature and discuss which downstream molecular effects are likely to be the drivers of the oncogenic and survival-prolonging properties of IDH1/2 mutations. We discuss interactions between mutant IDH1/2 inhibitors and conventional therapies. Understanding of the biochemical consequences of IDH1/2 mutations in oncogenesis and survival prolongation will yield valuable information for rational therapy design: it will tell us which oncogenic processes should be blocked and which “survivalogenic” effects should be retained.