t(10;14)(q24;q32) NFKB2/IGH

Review on t(10;14)(q24;q32) NFKB2/IGH, with data on clinics, and the genes involved

Could secondary flows make possible the cross-strait transport of passive floating organisms in the Strait of Gibraltar?

The Gibraltar Strait suffers an unprecedented invasion of the alien alga Rugulopteryx okamurae of North Pacific origin. Seemingly, algae first settled in the south shore around year 2015, probably following commercial exchanges with French ports, but there is no certainty that algae first colonized the south shore and then spread to the north one. The opposite could well have happened. Whatever the case, it spread with amazing rapidity over the whole area. Human-mediated vectors (algae attached to ship hulls or fishing nets) can be behind the spread from the shore initially settled to the opposite one. But secondary cross-strait flows within frictional Ekman boundary layers associated to the large along-strait velocity typical of this region could also have propitiated the connection without human intervention. Historical currentmeter profiles collected in the Strait show an intermediate layer of north-going cross-strait velocity near the interface of the mean baroclinic exchange, and an overlying surface layer of southward velocity, whose lower part overlaps the interfacial zone. The first one would facilitate south-to-north transport of algal fragments (or any other neutrally buoyant material) able to settle near the interface depth, while the second one would do the opposite. Cross-strait currents at this depth are of few cm/s, which implies crossing times of several days in low-illuminated conditions. Living organisms must be able to overcome these demanding conditions of darkness and maintain good photosynthetic activity after such period for a successful colonization. Rugulopteryx okamurae can do it.Universidad de Málaga. Campus de Excelencia Internacional del Mar CEIMAR

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement. Keywords: fetal brain abnormalities; fetal cytomegalovirus infection; fetal liver; magnetic resonance imaging; pregnancy

Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations

Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription. Here we report the development of vafidemstat (ORY-2001), a brain penetrant inhibitor of KDM1A and MAOB. ORY-2001 efficiently inhibits brain KDM1A at doses suitable for long term treatment, and corrects memory deficit as assessed in the novel object recognition testing in the Senescence Accelerated Mouse Prone 8 (SAMP8) model for accelerated aging and Alzheimer's disease. Comparison with a selective KDM1A or MAOB inhibitor reveals that KDM1A inhibition is key for efficacy. ORY-2001 further corrects behavior alterations including aggression and social interaction deficits in SAMP8 mice and social avoidance in the rat rearing isolation model. ORY-2001 increases the responsiveness of IEGs, induces genes required for cognitive function and reduces a neuroinflammatory signature in SAMP8 mice. Multiple genes modulated by ORY-2001 are differentially expressed in Late Onset Alzheimer's Disease. Most strikingly, the amplifier of inflammation S100A9 is highly expressed in LOAD and in the hippocampus of SAMP8 mice, and down-regulated by ORY-2001. ORY-2001 is currently in multiple Phase IIa studies

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women

Objective To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women. Methods A double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy. Results Treatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes. Conclusions ITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures

Progression of Late-Onset Stargardt Disease

PURPOSE. Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. METHODS. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset >= 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. RESULTS. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. CONCLUSIONS. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high

EUSEDcollab: a network of data from European catchments to monitor net soil erosion by water

As a network of researchers we release an open-access database (EUSEDcollab) of water discharge and suspended sediment yield time series records collected in small to medium sized catchments in Europe. EUSEDcollab is compiled to overcome the scarcity of open-access data at relevant spatial scales for studies on runoff, soil loss by water erosion and sediment delivery. Multi-source measurement data from numerous researchers and institutions were harmonised into a common time series and metadata structure. Data reuse is facilitated through accompanying metadata descriptors providing background technical information for each monitoring station setup. Across ten European countries, EUSEDcollab covers over 1600 catchment years of data from 245 catchments at event (11 catchments), daily (22 catchments) and monthly (212 catchments) temporal resolution, and is unique in its focus on small to medium catchment drainage areas (median=43km2, min=0.04km2, max=817km2) with applicability for soil erosion research. We release this database with the aim of uniting people, knowledge and data through the European Union Soil Observatory (EUSO)

Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis