Penicillium menonorum, a new species related to P. pimiteouiense

Penicillium menonorum is described as a new monoverticillate, non-vesiculate species that resembles P. restrictum and P. pimiteouiense. On the basis of phylogenetic analysis of DNA sequences from four loci, P. menonorum occurs in a clade with P. pimiteouiense, P. vinaceum, P. guttulosum, P. rubidurum, and P. parvum. Genealogical concordance analysis was applied to P. pimiteouiense and P. parvum, substantiating the phenotypically defined species. The species P. rubidurum, P. guttulosum, and P. menonorum were on distinct branches statistically excluded from inclusion in other species and have distinct phenotypes

One Fungus = One Name: DNA and fungal nomenclature twenty years after PCR

Some fungi with pleomorphic life-cycles still bear two names despite more than 20 years of molecular phylogenetics that have shown how to merge the two systems of classification, the asexual “Deuteromycota” and the sexual “Eumycota”. Mycologists have begun to flout nomenclatorial regulations and use just one name for one fungus. The International Code of Botanical Nomenclature (ICBN) must change to accommodate current practice or become irrelevant. The fundamental difference in the size of fungi and plants had a role in the origin of dual nomenclature and continues to hinder the development of an ICBN that fully accommodates microscopic fungi. A nomenclatorial crisis also looms due to environmental sequencing, which suggests that most fungi will have to be named without a physical specimen. Mycology may need to break from the ICBN and create a MycoCode to account for fungi known only from environmental nucleic acid sequence (i.e. ENAS fungi)

From Retinal Waves to Activity-Dependent Retinogeniculate Map Development

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca2+-activated K+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops

The Integrative Effects of Cognitive Reappraisal on Negative Affect: Associated Changes in Secretory Immunoglobulin A, Unpleasantness and ERP Activity

Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200–300 ms and 400–1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence

Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis

Background Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. Methods Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR. Mechanistic studies were performed in stable cell lines, mouse primary neurons and human embryonic stem cell-derived neurons. Loss and gain of function for TDP-43 and other microRNA pathway factors were modelled by siRNA-mediated knockdown and protein overexpression. Results We show that de novo paraspeckle assembly in spinal neurons and glial cells is a hallmark of both sporadic and familial ALS with TDP-43 pathology. Mechanistically, loss of TDP-43 but not its cytoplasmic accumulation or aggregation augments paraspeckle assembly in cultured cells. TDP-43 is a component of the microRNA machinery, and recently, paraspeckles have been shown to regulate pri-miRNA processing. Consistently, downregulation of core protein components of the miRNA pathway also promotes paraspeckle assembly. In addition, depletion of these proteins or TDP-43 results in accumulation of endogenous dsRNA and activation of type I interferon response which also stimulates paraspeckle formation. We demonstrate that human or mouse neurons in vitro lack paraspeckles, but a synthetic dsRNA is able to trigger their de novo formation. Finally, paraspeckles are protective in cells with compromised microRNA/dsRNA metabolism, and their assembly can be promoted by a small-molecule microRNA enhancer. Conclusions Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA

Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus

Spontaneous retinal activity (known as “waves”) remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON- or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species

Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis

BACKGROUND: Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but underlying mechanisms are unknown. The majority of ALS cases are characterized by TDP-43 proteinopathy. In current study we aimed to establish whether and how TDP-43 pathology may augment paraspeckle assembly. METHODS: Paraspeckle formation in human samples was analysed by RNA-FISH and laser capture microdissection followed by qRT-PCR. Mechanistic studies were performed in stable cell lines, mouse primary neurons and human embryonic stem cell-derived neurons. Loss and gain of function for TDP-43 and other microRNA pathway factors were modelled by siRNA-mediated knockdown and protein overexpression. RESULTS: We show that de novo paraspeckle assembly in spinal neurons and glial cells is a hallmark of both sporadic and familial ALS with TDP-43 pathology. Mechanistically, loss of TDP-43 but not its cytoplasmic accumulation or aggregation augments paraspeckle assembly in cultured cells. TDP-43 is a component of the microRNA machinery, and recently, paraspeckles have been shown to regulate pri-miRNA processing. Consistently, downregulation of core protein components of the miRNA pathway also promotes paraspeckle assembly. In addition, depletion of these proteins or TDP-43 results in accumulation of endogenous dsRNA and activation of type I interferon response which also stimulates paraspeckle formation. We demonstrate that human or mouse neurons in vitro lack paraspeckles, but a synthetic dsRNA is able to trigger their de novo formation. Finally, paraspeckles are protective in cells with compromised microRNA/dsRNA metabolism, and their assembly can be promoted by a small-molecule microRNA enhancer. CONCLUSIONS: Our study establishes possible mechanisms behind paraspeckle hyper-assembly in ALS and suggests their utility as therapeutic targets in ALS and other diseases with abnormal metabolism of microRNA and dsRNA

Methicillin Resistance Alters the Biofilm Phenotype and Attenuates Virulence in Staphylococcus aureus Device-Associated Infections

Clinical isolates of Staphylococcus aureus can express biofilm phenotypes promoted by the major cell wall autolysin and the fibronectin-binding proteins or the icaADBC-encoded polysaccharide intercellular adhesin/poly-N-acetylglucosamine (PIA/PNAG). Biofilm production in methicillin-susceptible S. aureus (MSSA) strains is typically dependent on PIA/PNAG whereas methicillin-resistant isolates express an Atl/FnBP-mediated biofilm phenotype suggesting a relationship between susceptibility to β-lactam antibiotics and biofilm. By introducing the methicillin resistance gene mecA into the PNAG-producing laboratory strain 8325-4 we generated a heterogeneously resistant (HeR) strain, from which a homogeneous, high-level resistant (HoR) derivative was isolated following exposure to oxacillin. The HoR phenotype was associated with a R602H substitution in the DHHA1 domain of GdpP, a recently identified c-di-AMP phosphodiesterase with roles in resistance/tolerance to β-lactam antibiotics and cell envelope stress. Transcription of icaADBC and PNAG production were impaired in the 8325-4 HoR derivative, which instead produced a proteinaceous biofilm that was significantly inhibited by antibodies against the mecA-encoded penicillin binding protein 2a (PBP2a). Conversely excision of the SCCmec element in the MRSA strain BH1CC resulted in oxacillin susceptibility and reduced biofilm production, both of which were complemented by mecA alone. Transcriptional activity of the accessory gene regulator locus was also repressed in the 8325-4 HoR strain, which in turn was accompanied by reduced protease production and significantly reduced virulence in a mouse model of device infection. Thus, homogeneous methicillin resistance has the potential to affect agr- and icaADBC-mediated phenotypes, including altered biofilm expression and virulence, which together are consistent with the adaptation of healthcare-associated MRSA strains to the antibiotic-rich hospital environment in which they are frequently responsible for device-related infections in immuno-compromised patients