Correction factors for Kac-Moody groups and tt-deformed root multiplicities

We study a correction factor for Kac-Moody root systems which arises in the theory of $p$-adic Kac-Moody groups. In affine type, this factor is known, and its explicit computation is the content of the Macdonald constant term conjecture. The data of the correction factor can be encoded as a collection of polynomials $m_\lambda \in \mathbb{Z}[t]$ indexed by positive imaginary roots $\lambda$. At $t=0$ these polynomials evaluate to the root multiplicities, so we consider $m_\lambda$ to be a $t$-deformation of $\mathrm{mult} (\lambda)$. We generalize the Peterson algorithm and the Berman-Moody formula for root multiplicities to compute $m_\lambda$. As a consequence we deduce fundamental properties of $m_\lambda$.Comment: 17 page

Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed

Effects of child long-term illness on maternal employment: longitudinal findings from the UK Millennium Cohort Study

Background: Maternal employment has increased in European countries, but levels of employment are lower among mothers whose children have a limiting long-term illness or disability. However, we do not know whether having a child with a limiting illness prevents take-up or maintenance of paid employment or whether ‘common causes’, such as lack of qualifications or maternal disability lead to both maternal unemployment and childhood illness. Longitudinal data have the potential to distinguish between these. Methods: We analyzed four waves (3, 5, 7 and 11 years) of the Millennium Cohort Study (MCS) to examine the relationship between childhood limiting illness and maternal employment, unadjusted and adjusted for covariates. Multinomial regression models were used to test the association between child illness and trajectories of maternal employment. Fixed effects models assessed whether a new report of a child illness increased the odds of a mother exiting employment. Results: At every wave, maternal employment was more likely if the child did not have a limiting illness. After adjustment for covariates, childhood illness was associated with risks of continuous non-employment (adjusted Relative Risk Ratio = 1.46 [Confidence Interval: 1.21, 1.76]) or disrupted employment (aRRR = 1.26 [CI: 1.06, 1.49]), compared with entering or maintaining employment. If a child developed a limiting long-term illness, the likelihood of their mother exiting employment increased (adjusted Odds Ratio = 1.27 [CI: 1.05, 1.54]). Conclusions: ‘Common causes’ did not fully account for the association between child illness and maternal employment. Having a child with a limiting illness potentially reduces maternal employment opportunities

Sexism of Fat: Is it sufficient to use only one sex in obesity research?

There is a weight issue weighing down the public health care systems across the world. Although obesity is prevalent in both males and females, the location of fat and impact on cardiometabolic health is strikingly different. These differences are apparent in the clinical setting, but there remains a bias towards using a single sex in mouse models to create simpler and cheaper experiments. The bias towards using a single sex in experiments skews the results and only offers translational research to one half of the human population. We examined sex differences and their effect on obesity by inducing obesity in both male and female mice by feeding them high fat diet (HFD) for 10 weeks. Mice were weighed weekly and after 10 weeks of HFD feeding, mice underwent metabolic tests to determine the impact of obesity. Male mice became obese after only 1 week of HFD feeding, however it took female mice 9 weeks of HFD feeding to become obese. Male mice were more susceptible to diabetes and male mice lost increased metabolic difference when fed HFD. This study highlights the importance of using both sexes to study obesity and associated diseases while highlighting novel differences in metabolism between sexes

Pathways to inequalities in child health

No abstract available.From birth, children living in disadvantaged socioeconomic circumstances (SECs) suffer from worse health than their more advantaged peers. The pathways through which SECs influence children’s health are complex and inter-related, but in general are driven by differences in the distribution of power and resources that determine the economic, material and psychosocial conditions in which children grow up. A better understanding of why children from more disadvantaged backgrounds have worse health and how interventions work, for whom and in what contexts, will help to reduce these unfair differences. Macro-level change is also required, including the reduction of child poverty through improved social security systems and employment opportunities, and continued investment in high-quality and accessible services (eg, childcare, key workers, children’s centres and healthy school environments). Child health professionals can play a crucial role by being mindful of the social determinants of health in their daily practice, and through advocating for more equitable and child-focussed resource allocation

Social inequalities in wheezing in children: findings from the UK Millennium Cohort Study

Wheezing in childhood is socially patterned, but it is unclear what factors explain the social differences.Regression analysis of the UK Millennium Cohort Study, based on 11 141 singleton children who participated at ages 9 months and 3, 5 and 7 years. Relative risk ratios (RRR) for early and persistent/relapsing wheeze were estimated using multinomial regression, according to measures of socioeconomic circumstances. Maternal, antenatal and early-life characteristics were assessed as potential mediators.Children of mothers with no educational qualifications were more likely to have both wheeze types, compared to children of mothers with degree-level qualifications (RRR 1.53, 95% CI 1.26-1.86 for early wheeze; 1.32 95% CI 1.04-1.67 for persistent/relapsing wheeze). Controlling for maternal age, smoking during pregnancy and breastfeeding removed the elevated risk of wheezing. Male sex, maternal age, body mass index, atopy, smoking during pregnancy, preterm birth, breastfeeding, exposure to other children and furry pets were independently associated with wheezing, but the pattern of association varied between wheezing types.In this representative UK cohort, adjustment for maternal smoking during pregnancy and breastfeeding removed the socioeconomic inequalities in common wheezing phenotypes. Policies to reduce the social gradient in these risk factors may reduce inequalities in wheezing and asthma

The Use of Biomimetic Hydrogels to Direct Stem Cell Differentiation for Tissue Engineering Applications

India Pursell is an undergraduate student in the School of Biological Sciences at Louisiana Tech University. Haley Barnett is a doctoral student in Molecular Science & Nanotechnology at Louisiana Tech University. Anna Whitehead is a research associate in Molecular Science & Nanotechnology at Louisiana Tech University. Mary Caldorera-Moore is an Assistant Professor in Biomedical Engineering, Molecular Science and Nanotechnology, and Nanosystems Engineering at Louisiana Tech University. Jamie Newman is an Assistant Professor in the School of Biological Sciences at Louisiana Tech University

“Orthotopic” ossiculum terminale persistens and atlantoaxial instability in a child less than 12 years of age: a case report and review of the literature

We report ossiculum terminale persistens associated with atlantoaxial instability in a child less than 12 years of age. Static and dynamic X-rays, thin-cut computed tomography with sagittal and coronal reconstructions, and magnetic resonance imaging of the cervical spine showed atlantoaxial instability and an “orthotopic” ossiculum terminale persistens. This pathologic state was differentiated from the primary ossification center at the tip of the odontoid, which normally is not expected to fuse with the body of the odontoid until the age of 12 years. The patient was taken to the operating room for a posterior instrumented fusion of C1 and C2. The patient has done well in short- and long-term follow-up

Fluorescent Labeling of Helminth Extracellular Vesicles Using an In Vivo Whole Organism Approach

In the last two decades, extracellular vesicles (EVs) from the three domains of life, Archaea, Bacteria and Eukaryotes, have gained increasing scientific attention. As such, the role of EVs in host-pathogen communication and immune modulation are being intensely investigated. Pivotal to EV research is the determination of how and where EVs are taken up by recipient cells and organs in vivo, which requires suitable tracking strategies including labelling. Labelling of EVs is often performed post-isolation which increases risks of non-specific labelling and the introduction of labelling artefacts. Here we exploited the inability of helminths to de novo synthesise fatty acids to enable labelling of EVs by whole organism uptake of fluorescent lipid analogues and the subsequent incorporation in EVs. We showed uptake of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (DOPE-Rho) in Anisakis spp. and Trichuris suis larvae. EVs isolated from the supernatant of Anisakis spp. labelled with DOPE-Rho were characterised to assess the effects of labelling on size, structure and fluorescence of EVs. Fluorescent EVs were successfully taken up by the human macrophage cell line THP-1. This study, therefore, presents a novel staining method that can be utilized by the EV field in parasitology and potentially across multiple species

Assembling a plug-and-play production line for combinatorial biosynthesis of aromatic polyketides in Escherichia coli

Polyketides are a class of specialised metabolites synthesised by both eukaryotes and prokaryotes. These chemically and structurally diverse molecules are heavily used in the clinic and include frontline antimicrobial and anticancer drugs such as erythromycin and doxorubicin. To replenish the clinicians’ diminishing arsenal of bioactive molecules, a promising strategy aims at transferring polyketide biosynthetic pathways from their native producers into the biotechnologically desirable host Escherichia coli. This approach has been successful for type I modular polyketide synthases (PKSs); however, despite more than 3 decades of research, the large and important group of type II PKSs has until now been elusive in E. coli. Here, we report on a versatile polyketide biosynthesis pipeline, based on identification of E. coli–compatible type II PKSs. We successfully express 5 ketosynthase (KS) and chain length factor (CLF) pairs—e.g., from Photorhabdus luminescens TT01, Streptomyces resistomycificus, Streptoccocus sp. GMD2S, Pseudoalteromonas luteoviolacea, and Ktedonobacter racemifer—as soluble heterodimeric recombinant proteins in E. coli for the first time. We define the anthraquinone minimal PKS components and utilise this biosynthetic system to synthesise anthraquinones, dianthrones, and benzoisochromanequinones (BIQs). Furthermore, we demonstrate the tolerance and promiscuity of the anthraquinone heterologous biosynthetic pathway in E. coli to act as genetically applicable plug-and-play scaffold, showing it to function successfully when combined with enzymes from phylogenetically distant species, endophytic fungi and plants, which resulted in 2 new-to-nature compounds, neomedicamycin and neochaetomycin. This work enables plug-and-play combinatorial biosynthesis of aromatic polyketides using bacterial type II PKSs in E. coli, providing full access to its many advantages in terms of easy and fast genetic manipulation, accessibility for high-throughput robotics, and convenient biotechnological scale-up. Using the synthetic and systems biology toolbox, this plug-and-play biosynthetic platform can serve as an engine for the production of new and diversified bioactive polyketides in an automated, rapid, and versatile fashion