Post break-up tectonic inversion across the southwestern cape of South Africa: new insights from apatite and zircon fission track thermochronometry

The south-west African margin is regarded as an example of a passive continental margin formed by continental rifting following a phase of lithospheric extension and thinning. Recent attention focused on this margin has included theoretical modelling studies of rift processes, plate kinematic studies of the opening geometry and timing, and empirical studies focused on documenting the crustal structure and offshore sedimentary record. Here, we examine the onshore geomorphic and tectonic response to rifting and breakup, with a specific focus on the SW Cape of South Africa. We present 75 new apatite and 8 new zircon fission track analyses from outcrop samples and onshore borehole profiles along the western margin of South Africa. The data are used to derive robust thermal histories that record two discrete phases of accelerated erosional cooling during the Early Cretaceous (150-130 Ma) and Late Cretaceous (100-80 Ma), respectively. Both periods of enhanced erosion are regional in extent, involved km-scale erosion, and extend well inland of the current escarpment zone, albeit with spatially variable intensity and style. The Late Cretaceous episode is also expressed more locally by tectonic reactivation and inversion of major faults causing km-scale differential displacement and erosion. The new AFT data do not exclude the possibility of modest surface uplift occurring during the Cenozoic, but they restrict the depth of regional Cenozoic erosion on the western margin to less than c. 1 km. The inferred pattern and chronology of erosion onshore is consistent with the key features and sediment accumulation patterns within the offshore Orange and Bredasdorp basins. It is suggested that the Late Cretaceous event was triggered by a combination of regional dynamic uplift augmented along the western margin and in the SW Cape by local tectonic forces arising from dextral displacement of the Falkland Plateau along the Falkland-Agulhas Fracture Zone

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review

<div><p>Type 1 diabetes is an autoimmune condition characterised by pancreatic beta cell destruction and absolute insulin deficiency. The strongest predictor of diabetes complications is glycaemic control and achieving HbA1c ≤ 7.0% is the primary management target. However, standard treatment appears to be lacking and adjunctive strategies require consideration. A systematic review was conducted to examine the effect of low-carbohydrate diets on type 1 diabetes management. Four databases were searched from inception until 28 March 2017: MEDLINE; CINAHL; Cochrane Library; and EMBASE. All primary studies containing a methods section (excluding cross-sectional) were included. Reports had to quantitatively measure the effect(s) of a dietary intervention or observed intake over at least two weeks where carbohydrate is below 45% total energy in adults and/or children with type 1 diabetes. The primary outcome was HbA1c and secondary outcomes were severe hypoglycaemia, total daily insulin, BMI, quality of life and mean daily glucose. Seventy-nine full-text articles were assessed for eligibility and nine were included (two randomised controlled trials, four pre-post interventions, two case-series, one case-report). Eight studies reported a mean change in HbA1c with a low-carbohydrate diet. Of these, four reported a non-significant change (P ≥ 0.05) and three reported statistically significant reductions (P < 0.05). Two studies reported severe hypoglycaemia, five reported total insulin, three reported BMI, and one reported blood glucose. Due to the significant heterogeneity of included studies, an overall effect could not be determined. This review presents all available evidence on low-carbohydrate diets for type 1 diabetes and suggests an urgent need for more primary studies.</p></div

PRISMA flow chart.

<p>PRISMA flow chart.</p

Characteristics of included studies.

<p>Characteristics of included studies.</p

Summary of findings table (GRADE) for primary outcome (HbA1c).

<p>Summary of findings table (GRADE) for primary outcome (HbA1c).</p

Effect of intervention and comparator diets on type 1 diabetes management outcomes (primary and secondary).

<p>Effect of intervention and comparator diets on type 1 diabetes management outcomes (primary and secondary).</p

PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells

The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent ApcMin/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly

Combination of two-dimensional gel electrophoresis and a fluorescent carboxyfluorescein-diacetate-labeled cisplatin analogue allows the identification of intracellular cisplatin-protein adducts

Cisplatin is one of the most widely used anticancer agents, but a major problem for successful chemotherapy is the development of drug resistance of tumor cells against cisplatin. Resistance to cisplatin is a multifactorial problem. A method to detect and identify intracellular cisplatin-protein adducts was developed using a fluorescent carboxyfluoresceindiacetate-labeled cisplatin analogue (CFDA-cisplatin), 2DE, and ESI-MS/MS. We identified several CFDA-cisplatin-protein adducts including members of the protein disulfide isomerase family (PDI). These are the first results of the detection of intracellular CFDA-cisplatin-protein adducts, which may help to understand the resistance mechanism of cisplatin