Non-destructive seed detection in mandarins: comparison of automatic threshold methods FLASH and COMSPIRA MRIs

Here, we review different methods for non-destructive horticultural produce size determination, focusing on electronic technologies capable of measuring fruit volume. The usefulness of produce size estimation is justified and a comprehensive classification system of the existing electronic techniques to determine dimensional size is proposed. The different systems identified are compared in terms of their versatility, precision and throughput. There is general agreement in considering that online measurement of axes, perimeter and projected area has now been achieved. Nevertheless, rapid and accurate volume determination of irregular-shaped produce, as needed for density sorting, has only become available in the past few years. An important application of density measurement is soluble solids content (SSC) sorting. If the range of SSC in the batch is narrow and a large number of classes are desired, accurate volume determination becomes important. A good alternative for fruit three-dimensional surface reconstruction, from which volume and surface area can be computed, is the combination of height profiles from a range sensor with a two-dimensional object image boundary from a solid-state camera (brightness image) or from the range sensor itself (intensity image). However, one of the most promising technologies in this field is 3-D multispectral scanning, which combines multispectral data with 3-D surface reconstruction

Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the β-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT–PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (β-catenin, protein kinase C, and C-Jun NH2-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis

The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance.

BACKGROUND: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of administration and low bioavailability are major clinical limitations. METHODS: Here, we studied the pharmacology of a new oral SERD, AZD9496, in a panel of in vitro and in vivo endocrine-sensitive and -resistant breast cancer models. RESULTS: In endocrine-sensitive models, AZD9496 inhibited cell growth and blocked ER activity in the presence or absence of oestrogen. In vivo, in the presence of oestrogen, short-term AZD9496 treatment, like fulvestrant, resulted in tumour growth inhibition and reduced expression of ER-dependent genes. AZD9496 inhibited cell growth in oestrogen deprivation-resistant and tamoxifen-resistant cell lines and xenograft models that retain ER expression. AZD9496 effectively reduced ER levels and ER-induced transcription. Expression analysis of short-term treated tumours showed that AZD9496 potently inhibited classic oestrogen-induced gene transcription, while simultaneously increasing expression of genes negatively regulated by ER, including genes potentially involved in escape pathways of endocrine resistance. CONCLUSIONS: These data suggest that AZD9496 is a potent anti-oestrogen that antagonises and degrades ER with anti-tumour activity in both endocrine-sensitive and endocrine-resistant models

Improving the efficiency and effectiveness of an industrial SARS-CoV-2 diagnostic facility.

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories

Effect of Larvae Treated with Mixed Biopesticide Bacillus thuringiensis - Abamectin on Sex Pheromone Communication System in Cotton Bollworm, Helicoverpa armigera

Third instar larvae of the cotton bollworm (Helicoverpa armigera) were reared with artificial diet containing a Bacillus thuringiensis - abamectin (BtA) biopesticide mixture that resulted in 20% mortality (LD(20)). The adult male survivors from larvae treated with BtA exhibited a higher percentage of “orientation” than control males but lower percentages of “approaching” and “landing” in wind tunnel bioassays. Adult female survivors from larvae treated with BtA produced higher sex pheromone titers and displayed a lower calling percentage than control females. The ratio of Z-11-hexadecenal (Z11–16:Ald) and Z-9-hexadecenal (Z9–16:Ald) in BtA-treated females changed and coefficients of variation (CV) of Z11–16:Ald and Z9–16:Ald were expanded compared to control females. The peak circadian calling time of BtA-treated females occurred later than that of control females. In mating choice experiment, both control males and BtA-treated males preferred to mate with control females and a portion of the Bt-A treated males did not mate whereas all control males did. Our Data support that treatment of larvae with BtA had an effect on the sex pheromone communication system in surviving H.armigera moths that may contribute to assortative mating

FGFR3 – a Central Player in Bladder Cancer Pathogenesis?

The identification of mutations in FGFR3 in bladder tumors in 1999 led to major interest in this receptor and during the subsequent 20 years much has been learnt about the mutational profiles found in bladder cancer, the phenotypes associated with these and the potential of this mutated protein as a target for therapy. Based on mutational and expression data, it is estimated that >80% of non-muscle-invasive bladder cancers (NMIBC) and ∼40% of muscle-invasive bladder cancers (MIBC) have upregulated FGFR3 signalling, and these frequencies are likely to be even higher if alternative splicing of the receptor, expression of ligands and changes in regulatory mechanisms are taken into account. Major efforts by the pharmaceutical industry have led to development of a range of agents targeting FGFR3 and other FGF receptors. Several of these have entered clinical trials, and some have presented very encouraging early results in advanced bladder cancer. Recent reviews have summarised the drugs and related clinical trials in this area. This review will summarise what is known about the effects of FGFR3 and its mutant forms in normal urothelium and bladder tumors, will suggest when and how this protein contributes to urothelial cancer pathogenesis and will highlight areas that may benefit from further study