HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

This article has been made available through the Brunel Open Access Publishing Fund.PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease.A Breast Cancer Campaign pilot grant awarded to E.M.H. supported this study. I.M.P. is supported by University of Hull HEFCE funding, and Royal Society and Breast Cancer Campaign pilot grants. S.A.E. is supported by ICR HEFCE funding and Cancer Research UK program grant C309/A11566. A.H. is supported by Brunel University HEFCE funding. E.M.H. is supported by a Cancer Research UK grant

Carbonic anhydrase IX expression is more predictive than prognostic in breast cancer

Contains fulltext : 52989.pdf (publisher's version ) (Closed access

Cobicistat as a Potential Booster of Ponatinib and Dasatinib Exposure in a CML Patient:A Case Study

The authors present a case of a 57-year-old patient with chronic myeloid leukemia who was treated with ponatinib and subsequently treated with dasatinib. The patient showed a major molecular response; however, the BCR-ABL1 signal increased with low ponatinib and dasatinib trough concentrations. Cobicistat was used as a pharmacokinetic booster to increase ponatinib and dasatinib exposure, as opposed to increasing the dose. However, ponatinib exposure was not sufficiently increased by cobicistat. The peak dasatinib concentration was successfully increased with cobicistat treatment. Dasatinib and cobicistat cotreatment induced a response in BCR-ABL1 PCR signal, was well tolerated, and led to a substantial reduction in drug costs.</p

Injection of photoelectrons into dense argon gas

The injection of photoelectrons in a gaseous or liquid sample is a widespread technique to produce a cold plasma in a weakly--ionized system in order to study the transport properties of electrons in a dense gas or liquid. We report here the experimental results of photoelectron injection into dense argon gas at the temperatureT=142.6 K as a function of the externally applied electric field and gas density. We show that the experimental data can be interpreted in terms of the so called Young-Bradbury model only if multiple scattering effects due to the dense environment are taken into account when computing the scattering properties and the energetics of the electrons.Comment: 18 pages, 10 figures, figure nr. 10 has been redrawn, to be submitted to Plasma Sources Science and Technolog

Combining Kangaroo Care and Live-Performed Music Therapy:Effects on Physiological Stability and Neurological Functioning in Extremely and Very Preterm Infants

Interventions such as kangaroo care (KC) and live-performed music therapy (LPMT), are increasingly used to facilitate stress reduction in neonates. This study aims to investigate the effect of combining the two on physiological responses and neurological functioning in very preterm infants. Infants received six sessions of LPMT. KC was added to one LPMT session. Physiological responses included heart rate, respiratory rate and oxygen saturation. We videotaped infants for 30 min before and after two sessions to assess general movements (GMs). We included 17 infants, gestational age median 26.0 weeks (IQR 25.6–30.6 weeks), of whom six were males. Combined interventions showed a decrease in heart rate from mean 164 bpm before to 157 bpm during therapy, p = 0.001. Oxygen saturation levels increased during combination therapy from median 91.4% to 94.5%, p = 0.044. We found no effects of LPMT or combined interventions on GMs. Infants with a postnatal age (PNA) 7 days. In conclusion, combining interventions is equally beneficial for physiological stability and neurological functioning as LPMT alone. Future studies should focus on the effects of this combination on parent-infant bonding

Universality in the Crossover between Edge Channel and Bulk Transport in the Quantum Hall Regime

We present a new theoretical approach for the integer quantum Hall effect, which is able to describe the inter-plateau transitions as well as the transition to the Hall insulator. We find two regimes (metallic and insulator like) of the top Landau level, in which the dissipative bulk current appears in different directions. The regimes are separated by a temperature invariant point.Comment: 4 page, 2 eps figures included, submitte

Recent distribution of Red-legged Partridge Alectoris rufa in Piedmont (North Western Italy): signs of recent spreading.

The red-legged partridge Alectoris rufa in Piedmont (NW Italy) is historically limited to the hilly and low-mountain areas of the southern half of the region, in particular lying in the Langhe and the Apennines on the Ligurian border, in the districts of Cuneo, Asti and Alessandria. In the Cuneo district, on the Maritime Alps, hybrid populations with Alectoris graeca were also known. The distribution of the species has been mapped in some occasions with the \u201cAtlases\u201d projects of the GPSO (Gruppo Piemontese Studi Ornitologici) and special enquiries. On this occasion we tried to update the geographical distribution of the species using data conferred by bird-watchers on www.regione.piemonte.it/aves/, managed by the GPSO, enquiries among hunters\u2019 organizations and specific field researches. The resulting distribution is shown on a 10 km square grid. The species shows signs of distribution dynamism, with the occupation of some lowland areas, where it was totally absent until the \u201890s. A little range expansion is noticeable also in the Western Monferrato. The situation seems to be more stable (or even declining) in the Langhe area and the species is now disappeared from the alpine border. In general we are seeing an areal contraction or density reduction on hills and mountains and an extension on lowlands. The observed changes seem to be attributable mainly to environmental and climate changes

Exploring failure of antimicrobial prophylaxis and pre-emptive therapy for transplant recipients:a systematic review

Objectives Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy. Setting This systematic review included prospective randomised controlled trials and prospective single-arm studies. Participants The studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018. Primary and secondary outcome measures Primary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death. Results From 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking. Conclusions Our results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review

Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

BACKGROUND: Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. CASE PRESENTATION: A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. CONCLUSION: We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block