Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change

The North Atlantic Oscillation (NAO) obtained using instrumental and documentary proxy predictors from Eurasia is found to be characterized by a quasi 60-year dominant oscillation since 1650. This pattern emerges clearly once the NAO record is time integrated to stress its comparison with the temperature record. The integrated NAO (INAO) is found to well correlate with the length of the day (since 1650) and the global surface sea temperature record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can be used as a good proxy for global climate change, and that a 60-year cycle exists in the global climate since at least 1700. Finally, the INAO ~60-year oscillation well correlates with the ~60- year oscillations found in the historical European aurora record since 1700, which suggests that this 60-year dominant climatic cycle has a solar-astronomical origin

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

Haploinsufficiency for Translation Elongation Factor eEF1A2 in Aged Mouse Muscle and Neurons Is Compatible with Normal Function

Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype "wasted" (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3-4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2

Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy

Background Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an autosomal dominant pattern. The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP. Methodology/Principal Findings A total of 58 subjects with a diagnosis of probable or definite CAA according to validated criteria were included in the present study. We sequenced the Aβ coding region of APP in 58 individuals and performed multiplex ligation-dependent probe amplification to determine APP gene dosage in 60. No patient harbored a known or novel APP mutation or gene duplication. The frequency of mutations investigated in the present study is estimated to range from 0% to 8% in individuals with probable CAA in the general population, based on the ascertained sample size. Conclusions/Significance We found no evidence that variants at loci associated with familial CAA play a role in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are unlikely to be seen in sporadic CAA patients. Therefore, our results do not support systematic genetic screening of CAA patients who lack a strong family history of hemorrhage or dementia.National Institute of Neurological Disorders and Stroke (U.S.) (grant K23NS042695)American Heart AssociationAmerican Stroke Association (Bugher Foundation for Stroke Prevention Research

Floral advertisement scent in a changing plant-pollinators market

Plant-pollinator systems may be considered as biological markets in which pollinators choose between different flowers that advertise their nectar/pollen rewards. Although expected to play a major role in structuring plant-pollinator interactions, community-wide patterns of flower scent signals remain largely unexplored. Here we show for the first time that scent advertisement is higher in plant species that bloom early in the flowering period when pollinators are scarce relative to flowers than in species blooming later in the season when there is a surplus of pollinators relative to flowers. We also show that less abundant flowering species that may compete with dominant species for pollinator visitation early in the flowering period emit much higher proportions of the generalist attractant β-ocimene. Overall, we provide a first community-wide description of the key role of seasonal dynamics of plant-specific flower scent emissions, and reveal the coexistence of contrasting plant signaling strategies in a plant-pollinator market

Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.https://nsuworks.nova.edu/hpd_medsci_faculty_books/1002/thumbnail.jp

Pathway-based expression profiling of benign prostatic hyperplasia and prostate cancer delineates an immunophilin molecule associated with cancer progression

Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to ARreactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis. Expression of FKBP52 was positively correlated with that of c-Myc. The functional cross-talk between c-Myc and FKBP52 was established using c-Myc specific-siRNA to LNCaP cells that resulted in reduction of FKBP52. A non-canonical E-box sequence housing a putative c-Myc binding site was detected on the FKBP4 promoter using in silico search. LNCaP cells transfected with the FKBP52 promoter cloned in pGL3 basic showed increased luciferase activity which declined considerably when the promoter-construct was co-transfected with c-Myc specific-siRNA. ChIP-PCR confirmed the binding of c-Myc with the conserved E-box located in the FKBP52 promoter. c-Myc downregulation concomitantly affected expression of FGF8. Since expression of FGF8 is controlled by AR, our study unveiled a novel functional axis between c-Myc, AR and FGF8 operating through FKBP52