3D Texture Analysis Reveals Imperceptible MRI Textural Alterations in the Thalamus and Putamen in Progressive Myoclonic Epilepsy Type 1, EPM1

Progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessively inherited neurodegenerative disorder characterized by young onset age, myoclonus and tonic-clonic epileptic seizures. At the time of diagnosis, the visual assessment of the brain MRI is usually normal, with no major changes found later. Therefore, we utilized texture analysis (TA) to characterize and classify the underlying properties of the affected brain tissue by means of 3D texture features. Sixteen genetically verified patients with EPM1 and 16 healthy controls were included in the study. TA was performed upon 3D volumes of interest that were placed bilaterally in the thalamus, amygdala, hippocampus, caudate nucleus and putamen. Compared to the healthy controls, EPM1 patients had significant textural differences especially in the thalamus and right putamen. The most significantly differing texture features included parameters that measure the complexity and heterogeneity of the tissue, such as the co-occurrence matrix-based entropy and angular second moment, and also the run-length matrix-based parameters of gray-level non-uniformity, short run emphasis and long run emphasis. This study demonstrates the usability of 3D TA for extracting additional information from MR images. Textural alterations which suggest complex, coarse and heterogeneous appearance were found bilaterally in the thalamus, supporting the previous literature on thalamic pathology in EPM1. The observed putamenal involvement is a novel finding. Our results encourage further studies on the clinical applications, feasibility, reproducibility and reliability of 3D TA.     

Proteolytic systems of lactic acid bacteria

Lactic acid bacteria (LAB) have a very long history of use in the manufacturing processes of fermented foods and a great deal of effort was made to investigate and manipulate the role of LAB in these processes. Today, the diverse group of LAB includes species that are among the best-studied microorganisms and proteolysis is one of the particular physiological traits of LAB of which detailed knowledge was obtained. The proteolytic system involved in casein utilization provides cells with essential amino acids during growth in milk and is also of industrial importance due to its contribution to the development of the organoleptic properties of fermented milk products. For the most extensively studied LAB, Lactococcus lactis, a model for casein proteolysis, transport, peptidolysis, and regulation thereof is now established. In addition to nutrient processing, cellular proteolysis plays a critical role in polypeptide quality control and in many regulatory circuits by keeping basal levels of regulatory proteins low and removing them when they are no longer needed. As part of the industrial processes, LAB are challenged by various stress conditions that are likely to affect metabolic activities, including proteolysis. While environmental stress responses of LAB have received increasing interest in recent years, our current knowledge on stress-related proteolysis in LAB is almost exclusively based on studies on L. lactis. This review provides the current status in the research of proteolytic systems of LAB with industrial relevance.     

Echovirus 1 infection depends on biogenesis of novel multivesicular bodies

Non-enveloped picornavirus echovirus 1 (EV1) clusters its receptor α2β1 integrin and causes their internalization and accumulation in α2β1 integrin enriched multivesicular bodies (α2-MVBs). Our results here show that these α2-MVBs are distinct from acidic late endosomes/lysosomes by several criteria: (i) live intra-endosomal pH measurements show that α2-MVBs are not acidic, (ii) they are not positive for the late endosomal marker LBPA or Dil-LDL internalized to lysosomes, and (iii) simultaneous stimulation of epidermal growth factor receptor (EGFR) and α2β1 integrin clustering leads to their accumulation in separate endosomes. EGFR showed downregulation between 15 min and 2 h, whereas accumulation of α2β1 integrin/EV1 led to an increase of integrin fluorescence in cytoplasmic vesicles further suggesting that EV1 pathway is separate from the lysosomal downregulation pathway. In addition, the results demonstrate the involvement of ESCRTs in the biogenesis of α2-MVBs. Overexpression of dominant-negative form of VPS4 inhibited biogenesis of α2-MVBs and efficiently prevented EV1 infection. Furthermore, α2-MVBs were positive for some members of ESCRTs such as Hrs, VPS37A and VPS24 and the siRNA treatment of TSG101, VPS37A and VPS24 inhibited EV1 infection. Our results show that the non-enveloped EV1 depends on biogenesis of novel multivesicular structures for successful infection.     

Occurrence of proteolytic inhibitors in various tissues of barley

Summary The three groups of proteolytic inhibitors present in resting barley grains, namely, trypsin inhibitors, Aspergillus-proteinase inhibitors, and inhibitors of endogenous proteinases, occur in both the embryo and the two endosperm tissues. There are pronounced quantitative differences, however. The three inhibitor activities in the embryo are, respectively, 6-, 0.1-, and 6-fold of those in the endosperm.During germination at 20° all inhibitor activities disappear from the endosperms in 4–5 days. Young rootlets and coleoptiles contain inhibitors of trypsin and Aspergillus proteinase, but these disappear after 4–5 days' germination. However, the trypsin inhibitor content per seedlings remains roughly constant through the whole period. The Aspergillus-proteinase inhibitors, in contrast, exhibit a pronounced increase of activity per seedling.No inhibitor activities were detected in leaves and roots at later stages of growth.The trypsin inhibitor which we have earlier purified from resting grains occurs exclusively in the two endospermal tissues and is immunologically entirely different from the trypsin inhibitors present in embryos and young seedlings.     

Genetic and Environmental Influences on the Tracking of Body Size from Birth to Early Adulthood

Objective: This study identified genetic and environmental influences on the tracking of body size from birth to 16 to 18.5 years of age. Research Methods and Procedures: Longitudinal information was collected from a nationally representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979) and their parents through questionnaires mailed when the twins were ages 16 and 18.5 years old. The sample included 702 monozygotic, 724 same‐sex dizygotic, and 762 opposite‐sex dizygotic sets of twins. The measures used were length, weight, ponderal index (kilograms per cubic meters), and gestational age at birth, and height, weight, and body mass index (kilograms per square meters) at 16 to 18.5 years of age. The changes in genetic and environmental influences on body size from birth to early adulthood were analyzed by quantitative genetic modeling. Results: The twins who had a higher weight or ponderal index at birth were taller and heavier in early adulthood, whereas those who were longer at birth were taller, but not heavier, later in life. Adult height was affected more by the birth size than body mass index. In the genetic modeling analyses, the genetic factors accounting for the variation of body size became more apparent with age, and both genetic and environmental influences on stature had a sizable carry‐over effect from birth to late adolescence, whereas for relative weight, the influences were more age‐specific. Discussion: The genetic and environmental architecture of body size changes from birth to adulthood. Even in monozygotic twins who share their genetic background, the initially larger twin tended to remain larger, demonstrating the long‐lasting effects of fetal environment on final body size.     

Maternal Smoking and the Risk of Cancer in Early Life – A Meta-Analysis

BackgroundIn spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases.ObjectivesThe aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations.MethodsIn a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated.ResultsSmoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02–1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05–1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring.ConclusionsAccording to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies.     

A molecular specificity code for the three mammalian KDEL receptors

AC-terminal KDEL-like motif prevents secretion of soluble endoplasmic reticulum (ER)–resident proteins. This motif interacts with KDEL receptors localized in the intermediate compartment and Golgi apparatus. Such binding triggers retrieval back to the ER via a coat protein I–dependent pathway. To date, two human KDEL receptors have been reported. Here, we report the Golgi localization of a third human KDEL receptor. Using a reporter construct system from a screen of 152 variants, we identified 35 KDEL-like variants that result in efficient ER localization but do not match the current Prosite motif for ER localization ([KRHQSA]-[DENQ]-E-L). We cloned 16 human proteins with one of these motifs and all were found in the ER. A subsequent screen by bimolecular fluorescence complementation determined the specificities of the three human KDEL receptors. Each KDEL receptor has a unique pattern of motifs with which it interacts. This suggests a specificity in the retrieval of human proteins that contain different KDEL variants.