Mutations in leaf starch metabolism modulate the diurnal root growth profiles of Arabidopsis thaliana

Roots of Arabidopsis thaliana exhibit stable diurnal growth profiles that are controlled by the circadian clock. Here we describe the effects of mutations in leaf starch metabolism on the diurnal root growth characteristics of Arabidopsis thaliana. High temporal and spatial resolution video imaging was performed to quantify the growth kinetics of Arabidopsis wild-type as well as pgm, sex1, mex1, dpe1 and dpe2 starch metabolism mutants grown in three different photoperiods. As a result, root growth patterns of all genotypes displayed characteristic modifications in their diurnal kinetics that were also affected by the photoperiod. To further investigate the role of starch derived substrate deficiency on root growth, the effect of 0.05% extracellular sucrose was studied in 12 h-12 h light-dark cycles.Key words: diurnal root growth kinetics, dpe1, dpe2, mex1, pgm, sex1, starch metabolism, video imagingRoot growth of Arabidopsis thaliana is highly rhythmic with respect to the time of the day.^1–3 In general, root growth rates increase at night while most of the light period is characterized by declining elongation rates. Since a slow oscillation in root growth rate with a periodicity of approximately 24 h persists in free running conditions it was demonstrated that the circadian clock mediates these daily fluctuations.¹ Root growth at night is fueled by the degradation of starch within the leaves. Thus, a correspondence between the time taken to degrade starch reserves and the length of the night is important to optimize growth in C-limiting conditions. Gibon et al. observed a strong correlation between the rate of starch degradation and the relative growth rate when Arabidopsis Col-0 was grown in a range of different photoperiods.⁴ Therefore, to avoid periods of C starvation at the end of the night the circadian clock was postulated to function as a timer that adjusts degradation of starch to the prevailing length of the night.^1,5Root growth strongly depends on the supply of sucrose from the leaves. To investigate the effects of substrate depletion on root elongation at night, 12-day-old seedlings of Col-0, pgm and sex1 growing in a 16 h photoperiod were previously investigated by digital time resolved video imaging.¹ As a result, the diel growth response was strongly modified in pgm and sex1 as compared to the wild-type. Both mutants showed a pronounced inhibition of growth during the night and a gradual recovery of growth during the light period. To substantiate these findings, we here report on the root elongation patterns of additional mutants in starch metabolism, e.g., mex1, dpe1 and dpe2 detected at different photoperiods and elevated external sucrose supply.     

Lymphopenia in COVID‐19: Therapeutic opportunities

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS‐CoV‐2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.     

Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia

Blood flow restoration to ischemic tissue is affected by various risk factors. The aim of this study was to examine gender effects on arteriogenesis and angiogenesis in a mouse ischemic hindlimb model. C57BL/6J mice were subjected to unilateral hindlimb ischemia. Flow recovery was less and hindlimb use impairment was greater in females. No gender difference in vessel number was found at baseline, although 7 days postsurgery females had fewer α-smooth muscle actin-positive vessels in the midpoint of the adductor region. Females had higher hindlimb vascular resistance, were less responsive to vasodilators, and were more sensitive to vasoconstrictors postligation. Western blotting showed that females had higher baseline levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the calf, while 7 days postligation males had higher levels of VEGF, eNOS, and phosphorylated vasodilator stimulated phosphoprotein. Females had less angiogenesis in a Matrigel plug assay and less endothelial cell proliferation in vitro. Females have impaired recovery of flow, a finding presumably caused by multiple factors including decreased collateral remodeling, less angiogenesis, impaired vasodilator response, and increased vasoconstrictor activity; our results also suggest the possibility that new collateral formation, from capillaries, is impaired in females.     

Alpha-synuclein interacts with Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases

The presynaptic protein α-synuclein (α-syn), particularly in its amyloid form, is widely recognized for its involvement in Parkinson disease (PD). Recent genetic studies reveal that mutations in the gene GBA are the most widespread genetic risk factor for parkinsonism identified to date. GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD). In this work, we investigated the possibility of a physical linkage between α-syn and GCase, examining both wild type and the GD-related N370S mutant enzyme. Using fluorescence and nuclear magnetic resonance spectroscopy, we determined that α-syn and GCase interact selectively under lysosomal solution conditions (pH 5.5) and mapped the interaction site to the α-syn C-terminal residues, 118-137. This α-syn-GCase complex does not form at pH 7.4 and is stabilized by electrostatics, with dissociation constants ranging from 1.2 to 22 μm in the presence of 25 to 100 mm NaCl. Intriguingly, the N370S mutant form of GCase has a reduced affinity for α-syn, as does the inhibitor conduritol-β-epoxide-bound enzyme. Immunoprecipitation and immunofluorescence studies verified this interaction in human tissue and neuronal cell culture, respectively. Although our data do not preclude protein-protein interactions in other cellular milieux, we suggest that the α-syn-GCase association is favored in the lysosome, and that this noncovalent interaction provides the groundwork to explore molecular mechanisms linking PD with mutant GBA alleles.     

Genomic dynamics of brown trout populations released to a novel environment

Population translocations occur for a variety of reasons, from displacement due to climate change to human‐induced transfers. Such actions have adverse effects on genetic variation and understanding their microevolutionary consequences requires monitoring. Here, we return to an experimental release of brown trout (Salmo trutta) in order to monitor the genomic effects of population translocations. In 1979, fish from each of two genetically (F _ST = 0.16) and ecologically separate populations were simultaneously released, at one point in time, to a lake system previously void of brown trout. Here, whole‐genome sequencing of pooled DNA (Pool‐seq) is used to characterize diversity within and divergence between the introduced populations and fish inhabiting two lakes downstream of the release sites, sampled 30 years later (c. 5 generations). Present results suggest that while extensive hybridization has occurred, the two introduced populations are unequally represented in the lakes downstream of the release sites. One population, which is ecologically resident in its original habitat, mainly contributes to the lake closest to the release site. The other population, migratory in its natal habitat, is genetically more represented in the lake further downstream. Genomic regions putatively under directional selection in the new habitat are identified, where allele frequencies in both established populations are more similar to the introduced population stemming from a resident population than the migratory one. Results suggest that the microevolutionary consequences of population translocations, for example, hybridization and adaptation, can be rapid and that Pool‐seq can be used as an initial tool to monitor genome‐wide effects.     

Sepantronium Bromide (YM155), A Small Molecule Survivin Inhibitor,Promotes Apoptosis by Induction of Oxidative Stress,Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study

Neurochemical Research - Cuprizone (cup) model targets oligodendrocytes (OLGs) degeneration and is frequently used for the mechanistic understanding of de- and remyelination. Improperly, this...     

Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

Background

The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011.

Methodology/Principal Findings

Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade.

Conclusions/Significance

In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.