Number,position, diameter and initial direction of growth of primary roots in Musa

To understand soil colonization by a root system, information is needed on the architecture of the root system. In monocotyledons, soil exploration is mainly due to the growth of adventitious primary roots. Primary root emergence in banana was quantified in relation to shoot and corm development. Root emergence kinetics were closely related to the development of aerial organs. Root position at emergence on the corm followed an asymptotic function of corm dry weight, so that the age of each root at a given time could be deduced from its position. Root diameter at emergence was related to the position of the roots on the corm, with younger roots being thicker than older ones. However, root diameters were not constant along a given root, but instead decreased with the distance to the base; roots appear to be conical in their basal and apical parts. Root growth directions at emergence were variable, but a high proportion of the primary roots emerged with a low angle to the horizontal. Further research is needed to evaluate whether these initial trajectories are conserved during root development. Results presented in this study are in good agreement with those reported for other monocotyledons such as maize and rice. They give quantitative information that will facilitate the development of models of root system architecture in banana.     

DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

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Highlights? DCC and netrin-1 are enriched at synapses in the adult mouse forebrain ? DCC is enriched in the PSD and regulates dendritic spine morphology ? LTP induction and memory formation require DCC expression by neurons ? DCC activation of Src is required for NMDAR-dependent LTP in adult CNS     

A Major Gene for Resting Metabolic Rate Unassociated with Body Composition: Results from the Québec Family Study

A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal — i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre- and post-adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non-Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.     

Sex-Dependent Alterations in Social Behaviour and Cortical Synaptic Activity Coincide at Different Ages in a Model of Alzheimer’s Disease

Besides memory deficits, Alzheimer’s disease (AD) patients suffer from neuropsychiatric symptoms, including alterations in social interactions, which are subject of a growing number of investigations in transgenic models of AD. Yet the biological mechanisms underlying these behavioural alterations are poorly understood. Here, a social interaction paradigm was used to assess social dysfunction in the triple-transgenic mouse model of AD (3xTg-AD). We observed that transgenic mice displayed dimorphic behavioural abnormalities at different ages. Social disinhibition was observed in 18 months old 3xTg-AD males compared to age and sex-matched control mice. In 3xTg-AD females, social disinhibition was present at 12 months followed by reduced social interactions at 18 months. These dimorphic behavioural alterations were not associated with alterations in AD neuropathological markers such as Aβ or tau levels in the frontal cortex. However, patch-clamp recordings revealed that enhanced social interactions coincided temporally with an increase in both excitatory and inhibitory basal synaptic inputs to layer 2–3 pyramidal neurons in the prefrontal cortex. These findings uncover a novel pattern of occurrence of psychiatric-like symptoms between sexes in an AD model. Our results also reveal that functional alterations in synapse activity appear as a potentially significant substrate underlying behavioural correlates of AD.     

Doppel is an N-glycosylated, glycosylphosphatidylinositol-anchored protein. Expression in testis and ectopic production in the brains of Prnp(0/0) mice predisposed to Purkinje cell loss

The Prnd gene encodes a homolog of the cellular prion protein (PrP(C)) called doppel (Dpl). Up-regulation of Prnd mRNA in two distinct lines of PrP gene ablated (Prnp(0/0)) mice, designated Rcm0 and Ngsk, is associated with death of Purkinje cells. Using recombinant Dpl expressed in Escherichia coli and mouse neuroblastoma cells we demonstrate that wild type (wt) Dpl, like PrP(C), adopts a predominantly alpha-helical conformation, forms intramolecular disulfide bonds, has two N-linked oligosaccharides, and is presented on the cell surface via a glycosylphosphatidylinositol anchor. Dpl protein was detected in testis of wt mice. Using Triton X-114 phase partitioning to enrich for glycosylphosphatidylinositol-anchored proteins, Dpl was detected in brain samples from Rcm0 Prnp(0/0) mice but was absent in equivalent samples from wt mice and ZrchI Prnp(0/0) mice, indicating that ectopic expression of this protein may cause cerebellar pathology in Rcm0 mice. Biochemical and structural similarities between PrP(C) and Dpl documented here parallel the observation that ataxic Ngsk Prnp(0/0) mice can be rescued by overexpression of wild-type PrP transgenes, and suggest that cell surface PrP(C) can antagonize the toxic effect of Dpl expressed in the central nervous system.     

Synthesis and in vitro evaluation of SG3227, a pyrrolobenzodiazepine dimer antibody-drug conjugate payload based on sibiromycin

A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro.     

Pandemic influenza due to pH1N1/2009 virus: estimation of infection burden in Reunion Island through a prospective serosurvey, austral winter 2009

Background

To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.

Methodology/Principal Findings

A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.

Conclusions

Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.     

CFD assessment of the effect of convective mass transport on the intracellular clearance of intracellular triglycerides in macrosteatotic hepatocytes

Donor livers available to transplant for patients with end-stage liver disease are in severe shortage. One possible avenue to expand the donor pool is to recondition livers that would be otherwise discarded due to excessive fat content. Severely steatotic livers (also known as fatty livers) are highly susceptible to ischemia-reperfusion injury and as a result, primary liver non-function post-transplantation. Prior studies in isolated perfused rat livers suggest that “defatting” may be possible in a timeframe of a few hours; thus, it is conceivable that fatty liver grafts could be recovered by machine perfusion to clear stored fat from the organ prior to transplantation. However, studies using hepatoma cells and adult hepatocytes made fatty in culture report that defatting may take several days. Because cell culture studies were done in static conditions, we hypothesized that the defatting kinetics are highly sensitive to flow-mediated transport of metabolites. To investigate this question, we experimentally evaluated the effect of increasing flow rate on the defatting kinetics of cultured HepG2 cells and developed an in silico combined reaction-transport model to identify possible rate-limiting steps in the defatting process. We found that in cultured fatty HepG2 cells, the time required to clear stored fat down to lean control cells can be reduced from 48 to 4–6 h by switching from static to flow conditions. The flow required resulted in a fluid shear of .008 Pa, which did not adversely affect hepatic function. The reaction-transport model suggests that the transport of l-carnitine, which is the carrier responsible for taking free fatty acids into the mitochondria, is the key rate-limiting process in defatting that was modulated by flow. Therefore, we can ensure higher levels of l-carnitine uptake by the cells by choosing flow rates that minimize the limiting mass transport while minimizing shear stress.