The genus Thoradonta in Thailand (Orthoptera: Tetrigidae: Scelimeninae) with description of two new species

The genus Thoradonta Hancock (Orthoptera: Tetrigidae: Scelimeninae) is newly reported from Thailand. Two new species of the genus, Thoradonta lativertexoides sp. nov. and Thoradonta spiculobaoides sp. nov., are described and illustrated with photographs and compared with similar species. A taxonomic review of the genus Thoradonta is provided and a key to all known species of the genus is given.     

WNK signalling pathways in blood pressure regulation

Hypertension (high blood pressure) is a major public health problem affecting more than a billion people worldwide with complications, including stroke, heart failure and kidney failure. The regulation of blood pressure is multifactorial reflecting genetic susceptibility, in utero environment and external factors such as obesity and salt intake. In keeping with Arthur Guyton’s hypothesis, the kidney plays a key role in blood pressure control and data from clinical studies; physiology and genetics have shown that hypertension is driven a failure of the kidney to excrete excess salt at normal levels of blood pressure. There is a number of rare Mendelian blood pressure syndromes, which have shed light on the molecular mechanisms involved in dysregulated ion transport in the distal kidney. One in particular is Familial hyperkalemic hypertension (FHHt), an autosomal dominant monogenic form of hypertension characterised by high blood pressure, hyperkalemia, hyperchloremic metabolic acidosis, and hypercalciuria. The clinical signs of FHHt are treated by low doses of thiazide diuretic, and it mirrors Gitelman syndrome which features the inverse phenotype of hypotension, hypokalemic metabolic alkalosis, and hypocalciuria. Gitelman syndrome is caused by loss of function mutations in the thiazide-sensitive Na/Cl cotransporter (NCC); however, FHHt patients do not have mutations in the SCL12A3 locus encoding NCC. Instead, mutations have been identified in genes that have revealed a key signalling pathway that regulates NCC and several other key transporters and ion channels in the kidney that are critical for BP regulation. This is the WNK kinase signalling pathway that is the subject of this review.     

Epistemic and methodological iteration in scientific research

A number of scholars have recently drawn attention to the importance of iteration in scientific research. This paper builds on these previous discussions by drawing a distinction between epistemic and methodological forms of iteration and by clarifying the relationships between them. As defined here, epistemic iteration involves progressive alterations to scientific knowledge claims, whereas methodological iteration refers to an interplay between different modes of research practice. While distinct, these two forms of iteration are related in important ways. Contemporary research on the biological effects of nanomaterials illustrates that methodological iteration can help to “initiate,” “equip,” and “stimulate” epistemic iteration.     

Approaches to Improving Consistency of Interval Fuzzy Preference Relations

This article introduces a consistency index for measuring the consistency level of an interval fuzzy preference relation（IFPR）.An approach is then proposed to construct an additive consistent IFPR from a given inconsistent IFPR.By using a weighted averaging method combining the original IFPR and the constructed consistent IFPR,a formula is put forward to repair an inconsistent IFPR to generate an IFPR with acceptable consistency.An iterative algorithm is subsequently developed to rectify an inconsistent IFPR and derive one with acceptable consistency and weak transitivity.The proposed approaches can not only improve consistency of IFPRs but also preserve the initial interval uncertainty information as much as possible.Numerical examples are presented to illustrate how to apply the proposed approaches.     

Functional genomics reveal that the serine synthesis pathway is essential in breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.     

Black hole growth in the early Universe is self-regulated and largely hidden from view

The formation of the first massive objects in the infant Universe remains impossible to observe directly and yet it sets the stage for the subsequent evolution of galaxies. Although some black holes with masses more than 10(9) times that of the Sun have been detected in luminous quasars less than one billion years after the Big Bang, these individual extreme objects have limited utility in constraining the channels of formation of the earliest black holes; this is because the initial conditions of black hole seed properties are quickly erased during the growth process. Here we report a measurement of the amount of black hole growth in galaxies at redshift z = 6-8 (0.95-0.7 billion years after the Big Bang), based on optimally stacked, archival X-ray observations. Our results imply that black holes grow in tandem with their host galaxies throughout cosmic history, starting from the earliest times. We find that most copiously accreting black holes at these epochs are buried in significant amounts of gas and dust that absorb most radiation except for the highest-energy X-rays. This suggests that black holes grew significantly more during these early bursts than was previously thought, but because of the obscuration of their ultraviolet emission they did not contribute to the re-ionization of the Universe.