Sequence analysis of a microsatellite and its flanking regions in intraspecific hybrids of grapevine (Vitis vinifera L.)

Microsatellite (MS) VVMD21 (BOWERS et al. 1999) was taken as a model to explore the molecular basis of polymorphism in a panel of 6 grapevine accessions (Vitis vinifera L.), consisting of Sangiovese and Cabernet Sauvignon and 4 F1 plants derived from crossing both varieties. The 12 alleles of both parents and the progeny were cloned and sequenced. The microsatellite repeat (AG)n>6 was found in each sequence, together with a poly-T rich region that showed irregularity. Furthermore, single nucleotide deletion or exchange (point mutations) were found in the microsatellite flanking regions

An extracellular transglutaminase is required for apple pollen tube growth

An extracellular form of the calcium-dependent protein-crosslinking enzyme TGase (transglutaminase) was demonstrated to be involved in the apical growth of Malus domestica pollen tube. Apple pollen TGase and its substrates were co-localized within aggregates on the pollen tube surface, as determined by indirect immunofluorescence staining and the in situ cross-linking of fluorescently labelled substrates. TGase-specific inhibitors and an anti-TGase monoclonal antibody blocked pollen tube growth, whereas incorporation of a recombinant fluorescent mammalian TGase substrate (histidine-tagged green fluorescent protein:His6– Xpr–GFP) into the growing tube wall enhanced tube length and germination, consistent with a role of TGase as a modulator of cell wall building and strengthening. The secreted pollen TGase catalysed the cross-linking of both PAs (polyamines) into proteins (released by the pollen tube) and His6-Xpr-GFP into endogenous or exogenously added substrates. A similar distribution of TGase activitywas observed in planta on pollen tubes germinating inside the style, consistent with a possible additional role for TGase in the interaction between the pollen tube and the style during fertilization

A phenomenological analysis of antiproton interactions at low energies

We present an optical potential analysis of the antiproton-proton interactions at low energies. Our optical potential is purely phenomenological, and has been parametrized on data recently obtained by the Obelix Collaboration at momenta below 180 MeV/c. It reasonably fits annihilation and elastic data below 600 MeV/c, and allows us for an evaluation of the elastic cross section and rho-parameter down to zero kinetic energy. Moreover we show that the mechanism that depresses antiproton-nucleus annihilation cross sections at low energies is present in antiproton-proton interactions too.Comment: 10 pages, 4 figure

Many-body current formula and current conservation for non-equilibrium fully interacting nanojunctions

We consider the electron transport properties through fully interacting nanoscale junctions beyond the linear-response regime. We calculate the current flowing through an interacting region connected to two interacting leads, with interaction crossing at the left and right contacts, by using a non-equilibrium Green's functions (NEGF) technique. The total current at one interface (the left one for example) is made of several terms which can be regrouped into two sets. The first set corresponds to a very generalised Landauer-like current formula with physical quantities defined only in the interacting central region and with renormalised lead self-energies. The second set characterises inelastic scattering events occurring in the left lead. We show how this term can be negligible or even vanish due to the pseudo-equilibrium statistical properties of the lead in the thermodynamic limit. The expressions for the different Green's functions needed for practical calculations of the current are also provided. We determine the constraints imposed by the physical condition of current conservation. The corresponding equation imposed on the different self-energy quantities arising from the current conservation is derived. We discuss in detail its physical interpretation and its relation with previously derived expressions. Finally several important key features are discussed in relation to the implementation of our formalism for calculations of quantum transport in realistic systems

Distinct endocytic pathways identified in tobacco pollen tubes using charged nanogold

In an attempt to dissect endocytosis in Nicotiana tabacum L. pollen tubes, two different probes \u2013 positively or negatively charged nanogold \u2013 were employed. The destiny of internalized plasma membrane domains, carrying negatively or positively charged residues, was followed at the ultrastructural level and revealed distinct endocytic pathways. Time-course experiments and electron microscopy showed internalization of subapical plasmamembrane domains that were mainly recycled to the secretory pathway through the Golgi apparatus and a second mainly degradative pathway involving plasma membrane retrieval at the tip. In vivo time-lapse experiments using FM4-64 combined with quantitative analysis confirmed the existence of distinct internalization regions. Ikarugamycin, an inhibitor of clathrin-dependent endocytosis, allowed us to further dissect the endocytic process: electron microscopy and time-lapse studies suggested that clathrin-dependent endocytosis occurs in the tip and subapical regions, because recycling of positively charged nanogold to the Golgi bodies and the consignment of negatively charged nanogold to vacuoles were affected. However, intact positively charged-nanogold transport to vacuoles supports the idea that an endocytic pathway that does not require clathrin is also present in pollen tubes

Phase 1 dose-escalation study of S-222611, an oral reversible dual tyrosine kinase inhibitor of EGFR and HER2, in patients with solid tumours.

BACKGROUND: S-222611 is a reversible inhibitor of EGFR, HER2 and HER4 with preclinical activity in models expressing these proteins. We have performed a Phase 1 study to determine safety, maximum tolerated dose (MTD), pharmacokinetic profile (PK) and efficacy in patients with solid tumours expressing EGFR or HER2. PATIENTS AND METHODS: Subjects had advanced tumours not suitable for standard treatment, expressing EGFR or HER2, and/or with amplified HER2. Daily oral doses of S-222611 were escalated from 100mg to 1600 mg. Full plasma concentration profiles for drug and metabolites were obtained. RESULTS: 33 patients received S-222611. It was well tolerated, and the most common toxicities, almost all mild (grade 1 or 2), were diarrhoea, fatigue, rash and nausea. Only two dose-limiting toxicities occurred (diarrhoea and rash), which resolved on interruption. MTD was not reached. Plasma exposure increased with dose up to 800 mg, exceeding levels eliciting pre-clinical responses. The plasma terminal half-life was more than 24h, supporting once daily dosing. Responses were seen over a wide range of doses in oesophageal, breast and renal tumours, including a complete clinical response in a patient with HER2-positive breast carcinoma previously treated with lapatinib and trastuzumab. Four patients have remained on treatment for more than 12 months. Downregulation of pHER3 was seen in paired tumour biopsies from a responding patient. CONCLUSIONS: Continuous daily oral S-222611 is well tolerated, modulates oncogenic signalling, and has significant antitumour activity. The recommended Phase 2 dose, based on PK and efficacy, is 800 mg/day.The authors acknowledge financial support from the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust (and NIHR Clinical Research Facility), and to The University of Cambridge and Cambridge University Hospital NHS Foundation Trust. Cambridge, King’s College London, and Newcastle are Experimental Cancer Medicine Centres.This is the accepted manuscript. The final version is available from http://www.sciencedirect.com/science/article/pii/S0959804914010922

Towards Graphene Nanoribbon-based Electronics

The successful fabrication of single layer graphene has greatly stimulated the progress of the research on graphene. In this article, focusing on the basic electronic and transport properties of graphene nanoribbons (GNRs), we review the recent progress of experimental fabrication of GNRs, and the theoretical and experimental investigations of physical properties and device applications of GNRs. We also briefly discuss the research efforts on the spin polarization of GNRs in relation to the edge states.Comment: 9pages,10figure

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom

\ua9 The Author(s) 2024.Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. Results: 132 pts were included. Median age was 56 years (28–91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5–6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience