Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

Open networks of infinite server queues with non-homogeneous multivariate batch Poisson arrivals

In this paper, we consider the occupancy distribution for an open network of infinite server queues with multivariate batch arrivals following a non-homogeneous Poisson process, and general service time distributions. We derive a probability generating function for the transient occupancy distribution of the network, and prove that it is necessary and sufficient for ergodicity that the expected occupancy time for each batch be finite. Further, we recover recurrence relations for the transient probability mass function formulated in terms of a distribution obtained by compounding the batch size with a multinomial distribution

Evanescent character of the repulsive thermal Casimir force

The physical origin of the negative thermal correction to the Casimir force between metals is clarified. For this purpose the asymptotic behavior of the thermal Casimir force is analyzed at large and small distances in the real frequency representation. Contributions from propagating and evanescent waves are considered separately. At large distances they cancel each other in substantial degree so that only the attractive Lifshitz limit survives. At smaller separations the repulsive evanescent contribution of s-polarization dominates in the case of two metals or a metal and a high-permittivity dielectric. Common origin and order of magnitude of the repulsion in these two cases demonstrate naturalness of the controversial large thermal correction between metals.Comment: to be published in Phys. Rev.

Inversion of Gamow's Formula and Inverse Scattering

We present a pedagogical description of the inversion of Gamow's tunnelling formula and we compare it with the corresponding classical problem. We also discuss the issue of uniqueness in the solution and the result is compared with that obtained by the method of Gel'fand and Levitan. We hope that the article will be a valuable source to students who have studied classical mechanics and have some familiarity with quantum mechanics.Comment: LaTeX, 6 figurs in eps format. New abstract; notation in last equation has been correcte

KLF6 and STAT3 Co-Occupy Regulatory DNA and Functionally Synergize to Promote Axon Growth in CNS Neurons

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction between KLF6 and a second transcription factor, STAT3, and genome-wide footprinting using ATAC-Seq data confirmed frequent co-occupancy. Co-expression of the two factors yielded a synergistic elevation of neurite growth in vitro. These data clarify the transcriptional control of axon growth and point the way toward novel interventions to promote CNS regeneration

Developmental Chromatin Restriction of Pro‐Growth Gene Networks Acts as an Epigenetic Barrier to Axon Regeneration in Cortical Neurons

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age‐dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome‐wide maps of chromatin accessibility. When applied to the developing cortex, this pipeline detected overall closure of chromatin in sub‐networks of genes associated with axon growth. We next analyzed mature CNS neurons that were supplied with various pro‐regenerative transcription factors. Unlike prior results with SOX11 and KLF7, here we found that neither JUN nor an activated form of STAT3 promoted substantial corticospinal tract regeneration. Correspondingly, chromatin accessibility in JUN or STAT3 target genes was substantially lower than in predicted targets of SOX11 and KLF7. Finally, we used the pipeline to predict pioneer factors that could potentially relieve chromatin constraints at growth‐associated loci. Overall this integrated analysis substantiates the hypothesis that dynamic chromatin accessibility contributes to the developmental decline in axon growth ability and influences the efficacy of pro‐regenerative interventions in the adult, while also pointing toward selected pioneer factors as high‐priority candidates for future combinatorial experiments

The Stability of an Isentropic Model for a Gaseous Relativistic Star

We show that the isentropic subclass of Buchdahl's exact solution for a gaseous relativistic star is stable and gravitationally bound for all values of the compactness ratio $u [\equiv (M/R)$, where $M$ is the total mass and $R$ is the radius of the configuration in geometrized units] in the range, $0 < u \leq 0.20$, corresponding to the {\em regular} behaviour of the solution. This result is in agreement with the expectation and opposite to the earlier claim found in the literature.Comment: 9 pages (including 1 table); accepted for publication in GR

Strengthening the integration of midwifery in health systems; a leader-to-leader collaboration

Barriers and facilitators for quality midwifery care exist on different levels in the health systems. After decades of challenges and varied degrees of success, a stakeholder leader-to-leader collaboration could provide added value through knowledge sharing on how to integrate the midwifery cadre into an existing health system. Initiated by The Midwifery Society of Nepal, Dalarna University Sweden and MAMTA - Health Institute for Mother and Child India, a research network focusing midwifery has been formed. The background, purpose and activities of this network has been described in this News and Events paper