Kinetic Benchmarking Reveals the Competence of Prenyl Groups in Ring-Closing Metathesis

A series of prenyl-containing malonates are kinetically benchmarked against the standard allyl-containing congeners using a ruthenium benzylidene precatalyst for ring-closing metatheses. The prenyl grouping is found to be a superior acceptor olefin compared to an allyl group in RCM processes with ruthenium alkylidenes derived from terminal alkenes. The prenyl group is also found to be a highly competent acceptor for a ruthenium alkylidene derived from a 1,1-disubstituted olefin in a RCM process

The impact of the COVID-19 pandemic on the relationship between physical activity levels and mental health in UK university students

Aim: Physical activity (PA) is widely acknowledged as a cost-effective strategy to support mental health in students. However, the COVID-19 pandemic’s disruptive influence raises questions about how the relationship between PA and student mental health may have evolved. Therefore, the present study explored this relationship before, during and after the pandemic. Methods: A repeated cross-sectional design was employed with survey data collected annually (2019–2022) in term one (October) at an English university. Mental well-being was evaluated using the Short Warwick-Edinburgh Mental Well-being Scale and weekly moderate to vigorous physical activity (MVPA) measured in 6,250 students. Pearson’s Product Moment Correlation tests were used to assess the correlation between mental well-being and MVPA for each year. Results: There was a weak (r = 0.14–0.19, p < 0.001) positive correlation between mental well-being and MVPA for each year. This relationship was stronger for males compared to females in 2020 (Z = 1.02, p < 0.01) and 2022 (Z = 3.56, p < 0.001). Conclusion: The consistent correlation between mental well-being and MVPA suggests that the pandemic did not alter the discernible link between the two variables, emphasising the importance of PA for student mental health even during unprecedented circumstances

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Light dark matter in the NMSSM: upper bounds on direct detection cross sections

In the Next-to-Minimal Supersymmetric Standard Model, a bino-like LSP can be as light as a few GeV and satisfy WMAP constraints on the dark matter relic density in the presence of a light CP-odd Higgs scalar. We study upper bounds on the direct detection cross sections for such a light LSP in the mass range 2-20 GeV in the NMSSM, respecting all constraints from B-physics and LEP. The OPAL constraints on e^+ e^- -> \chi^0_1 \chi^0_i (i > 1) play an important role and are discussed in some detail. The resulting upper bounds on the spin-independent and spin-dependent nucleon cross sections are ~ 10^{-42} cm^{-2} and ~ 4\times 10^{-40} cm^{-2}, respectively. Hence the upper bound on the spin-independent cross section is below the DAMA and CoGeNT regions, but could be compatible with the two events observed by CDMS-II.Comment: 17 pages, 3 figure

Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy

Structural Insights into Triglyceride Storage Mediated by Fat Storage-Inducing Transmembrane (FIT) Protein 2

Fat storage-Inducing Transmembrane proteins 1 & 2 (FIT1/FITM1 and FIT2/FITM2) belong to a unique family of evolutionarily conserved proteins localized to the endoplasmic reticulum that are involved in triglyceride lipid droplet formation. FIT proteins have been shown to mediate the partitioning of cellular triglyceride into lipid droplets, but not triglyceride biosynthesis. FIT proteins do not share primary sequence homology with known proteins and no structural information is available to inform on the mechanism by which FIT proteins function. Here, we present the experimentally-solved topological models for FIT1 and FIT2 using N-glycosylation site mapping and indirect immunofluorescence techniques. These methods indicate that both proteins have six-transmembrane-domains with both N- and C-termini localized to the cytosol. Utilizing this model for structure-function analysis, we identified and characterized a gain-of-function mutant of FIT2 (FLL(157-9)AAA) in transmembrane domain 4 that markedly augmented the total number and mean size of lipid droplets. Using limited-trypsin proteolysis we determined that the FLL(157-9)AAA mutant has enhanced trypsin cleavage at K86 relative to wild-type FIT2, indicating a conformational change. Taken together, these studies indicate that FIT2 is a 6 transmembrane domain-containing protein whose conformation likely regulates its activity in mediating lipid droplet formation

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

An EGF-like Protein Forms a Complex with PfRh5 and Is Required for Invasion of Human Erythrocytes by Plasmodium falciparum

Invasion of erythrocytes by Plasmodium falciparum involves a complex cascade of protein-protein interactions between parasite ligands and host receptors. The reticulocyte binding-like homologue (PfRh) protein family is involved in binding to and initiating entry of the invasive merozoite into erythrocytes. An important member of this family is PfRh5. Using ion-exchange chromatography, immunoprecipitation and mass spectroscopy, we have identified a novel cysteine-rich protein we have called P. falciparum Rh5 interacting protein (PfRipr) (PFC1045c), which forms a complex with PfRh5 in merozoites. Mature PfRipr has a molecular weight of 123 kDa with 10 epidermal growth factor-like domains and 87 cysteine residues distributed along the protein. In mature schizont stages this protein is processed into two polypeptides that associate and form a complex with PfRh5. The PfRipr protein localises to the apical end of the merozoites in micronemes whilst PfRh5 is contained within rhoptries and both are released during invasion when they form a complex that is shed into the culture supernatant. Antibodies to PfRipr1 potently inhibit merozoite attachment and invasion into human red blood cells consistent with this complex playing an essential role in this process

Cognitive and environmental predictors of early literacy skills

Not all young children benefit from book exposure in preschool age. It is claimed that the ability to hold information in mind (short-term memory), to ignore distraction (inhibition), and to focus attention and stay focused (sustained attention) may have a moderating effect on children’s reactions to the home literacy environment. In a group of 228 junior kindergarten children with a native Dutch background, with a mean age of 54.29 months (SD = 2.12 months), we explored therefore the relationship between book exposure, cognitive control and early literacy skills. Parents filled in a HLE questionnaire (book sharing frequency and an author recognition checklist as indicator of parental leisure reading habits), and children completed several tests in individual sessions with the researcher (a book-cover recognition test, PPVT, letter knowledge test, the subtests categories and patterns of the SON, and cognitive control measures namely digit span of the KABC, a peg tapping task and sustained attention of the ANT). Main findings were: (1) Children’s storybook knowledge mediated the relationship between home literacy environment and literacy skills. (2) Both vocabulary and letter knowledge were predicted by book exposure. (3) Short-term memory predicted vocabulary over and above book exposure. (4) None of the cognitive control mechanisms moderated the beneficial effects of book exposure

Detailed Mitochondrial Phenotyping by High Resolution Metabolomics

Mitochondrial phenotype is complex and difficult to define at the level of individual cell types. Newer metabolic profiling methods provide information on dozens of metabolic pathways from a relatively small sample. This pilot study used “top-down” metabolic profiling to determine the spectrum of metabolites present in liver mitochondria. High resolution mass spectral analyses and multivariate statistical tests provided global metabolic information about mitochondria and showed that liver mitochondria possess a significant phenotype based on gender and genotype. The data also show that mitochondria contain a large number of unidentified chemicals