The low TN : TP ratio, a cause or a result of Microcystis blooms?

An enclosure experiment in the shallow, subtropical Lake Donghu, China, was performed in the summer of 2001 to examine the effect of TN:TP (total phosphorus) ratios and P-reduction on the occurrence of Microcysitis blooms. The treatments were performed with enough amounts of N but with different amounts of P in the water column and sediment. Microcystis blooms occurred in the enclosures either with an initial TN:TP <29 or TN:TP >29 where the nutrients (N, P) were high enough. Microcysitis blooms never occurred in the treatments with low P concentration in spite of the presence of sufficient N. The P-rich sediments served as an important source for the P supply in the water column, and such a process was activated greatly by the outburst of Microcystis blooms which pumped up selectively P from the sediments and thus decreased the TN:TP ratios. Therefore, the low TN:TP ratio is not a cause but rather a result of Microcystis blooms. (C) 2002 Elsevier Science Ltd. All rights reserved.

Coal-burning roasted corn and chili as the cause of dental fluorosis for children in southwestern China

To find the pathologic cause of the children's dental fluorosis in southwestern China, diet structure before the age of 6 and prevalence rate of dental fluorosis (DF) of 405 children were investigated, and the fluorine and arsenic content of several materials were determined. The prevalence rate of DF of children living on roasted corn before the age of 6 is 100% with nearly 95% having the mild to severe DF; while that of children living on non-roasted corn or rice is less than 5% with all having very mild DF. The average fluorine and arsenic concentration are 20.26 mg/kg and 0.249 mg/kg in roasted corn, which are about 16 times and 35 times more than in non-roasted corn, respectively. The average fluorine concentration is 78 mg/kg in coal, 1116 mg/kg in binder clay and 313 mg/kg in briquette (coal mixed with clay). The average arsenic concentration of coal is 5.83 mg/kg, the binder clay is 20.94 mg/kg, with 8.52 mg/kg in the briquette. Living on roasted corn and chili is the main pathologic cause of endemic fluorosis in southwestern China. The main source of fluorine and arsenic pollution of roasted corn and chill is the briquette of coal and binder clay. (C) 2010 Elsevier B.V. All rights reserved.

The paleoclimatic events and cause in the Okinawa Trough during 50 kaBP

Planktonic foraminiferal delta O-18 record for core DGKS9603 from the Okinawa Trough shows a series of climatic fluctuations and sudden cooling events in short time scale during 50 kaBP, which appear to correlate closely to the Younger Dryas and Heinrich events H1-5 recorded in Chinese loess, the South China Sea, the North Atlantic cores and the Greenland ice cores. Three polarity reversal events, correlating to Gothenburg, Mungo and Laschamp events, approximately correspond to Heinrich events H1, H3 and H5 respectively, which could be a cause of global climate changes. The delta O-18 curve of the Okinawa Trough is well associated with the grain size record of the Lijiayuan loess profile in northwestern China and is somewhat different from the climate fluctuations documented in the Greenland ice cores. These correlation results indicate that regional factors play an important role in controlling the climate changes in the East Asia, and the East Asian Monsoon could be the prominent regional controlling factor.

Causes of a Divided Discipline: Rethinking the Concept of Cause in International Relations theory

Kurki, M. (2006). Causes of a Divided Discipline: Rethinking the Concept of Cause in International Relations theory. Review of International Studies, 32 (2), 189-216. RAE2008

In Common Cause: The NATO Multilateral Force and Mixed-Manning Demonstration on USS Claude V. Ricketts, 1964-1965

Priest, A. (2005). In Common Cause: The NATO Multilateral Force and Mixed-Manning Demonstration on USS Claude V. Ricketts, 1964-1965. Journal of Military History, 69 (3), 759-789. RAE2008

Rallying to a cause: the plays of Zakes Mda 1979-1989

Zakes Mda, dubbed one of South Africa's most prolific playwrights, produced his richest and most powerful theatre work during the 70s and 80s. Ironically, it is only in the 90s that he has been acknowledged in his own country as one of its foremost dramatists - ironic since he has recently moved away from drama into the realms of fiction. Fortunately Mda has accumulated a worthy canon of dramatic works, spanning radio and film, as well as theatre, and there is no reason to believe that he will not return to play writing. Mda has worked extensively in theatre in various capacities but most notably in the area of theatre-for-development. For example, he worked as director with Maratholi Travelling Theatre in Lesotho, an experience which contributed, in part, towards his book "When People Play People: Development Communication Through Theatre". Mda's plays have been produced in the United States, Britain, Spain, France and Russia as well as in southern Africa. "The Nun's Romantic Story" has been translated into Castilian and Catalan and "We Shall Sing for the Fatherland" and "Dark Voices Ring" have both been translated into Russian and French. In South Africa he won the Merit Award of the Amstel Playwright of the Year Society for "We Shall Sing for the Fatherland" in 1978 and in 1979 he was Amstel Playright of the Year for "The Hill". For his novel "She Plays with the Darkness", he won the Sanlam Literary Award in 1995.

VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD.

VCP (VCP/p97) is a ubiquitously expressed member of the AAA(+)-ATPase family of chaperone-like proteins that regulates numerous cellular processes including chromatin decondensation, homotypic membrane fusion and ubiquitin-dependent protein degradation by the proteasome. Mutations in VCP cause a multisystem degenerative disease consisting of inclusion body myopathy, Paget disease of bone, and frontotemporal dementia (IBMPFD). Here we show that VCP is essential for autophagosome maturation. We generated cells stably expressing dual-tagged LC3 (mCherry-EGFP-LC3) which permit monitoring of autophagosome maturation. We determined that VCP deficiency by RNAi-mediated knockdown or overexpression of dominant-negative VCP results in significant accumulation of immature autophagic vesicles, some of which are abnormally large, acidified and exhibit cathepsin B activity. Furthermore, expression of disease-associated VCP mutants (R155H and A232E) also causes this autophagy defect. VCP was found to be essential to autophagosome maturation under basal conditions and in cells challenged by proteasome inhibition, but not in cells challenged by starvation, suggesting that VCP might be selectively required for autophagic degradation of ubiquitinated substrates. Indeed, a high percentage of the accumulated autophagic vesicles contain ubiquitin-positive contents, a feature that is not observed in autophagic vesicles that accumulate following starvation or treatment with Bafilomycin A. Finally, we show accumulation of numerous, large LAMP-1 and LAMP-2-positive vacuoles and accumulation of LC3-II in myoblasts derived from patients with IBMPFD. We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis.

Dust accumulation in the canopy: a potential cause of dental microwear in primates.

Dental microwear researchers consider exogenous grit or dust to be an important cause of microscopic wear on primate teeth. No study to date has examined the accumulation of such abrasives on foods eaten by primates in the forest. This investigation introduces a method to collect dust at various heights in the canopy. Results from dust collection studies conducted at the primate research stations at Ketambe in Indonesia, and Hacienda La Pacifica in Costa Rica indicate that 1) grit collects throughout the canopy in both open country and tropical rain forest environments; and 2) the sizes and concentrations of dust particles accumulated over a fixed period of time differ depending on site location and season of investigation. These results may hold important implications for the interpretation of microwear on primate teeth.

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

PURPOSE: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. METHODS: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. RESULTS: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. CONCLUSION: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome.

HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells

BACKGROUND: Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. Therefore, elucidating the mechanisms by which HDACi trigger differentiation, cell cycle arrest, or apoptosis of cancer cells could inform development of more targeted therapies. We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process. RESULTS: We identified several thousand specific regulatory elements [~10 % of total DNase I-hypersensitive (DHS) sites] that become significantly more or less accessible with sodium butyrate or suberanilohydroxamic acid treatment. Most of the differential DHS sites display hallmarks of enhancers, including being enriched for non-promoter regions, associating with nearby gene expression changes, and increasing luciferase reporter expression in K562 cells. Differential DHS sites were enriched for key hematopoietic lineage transcription factor motifs, including SPI1 (PU.1), a known pioneer factor. We found PU.1 increases binding at opened DHS sites with HDACi treatment by ChIP-seq, but PU.1 knockdown by shRNA fails to block the chromatin accessibility and expression changes. A machine-learning approach indicates H3K27me3 initially marks PU.1-bound sites that open with HDACi treatment, suggesting these sites are epigenetically poised. CONCLUSIONS: We find HDACi treatment of K562 cells results in site-specific chromatin remodeling at epigenetically poised regulatory elements. PU.1 shows evidence of a pioneer role in this process by marking poised enhancers but is not required for transcriptional activation.

On treating the symptoms and not the cause: reflections on the Dangerous Dogs Act

The experience of saving a dog that later turned out to be a Pit Bull and therefore banned under the Dangerous Dogs Act 1991, made me investigate the Act and its implications. The Act is not built on evidence and by compiling results from different studies on dog bites and breed‐specific legislation in different countries the conclusion is that there is not much empirical support for breed bans either. ‘Dangerous breeds’ do not bite more frequently than German Shepherds and directing legislation towards certain breeds deemed as ‘dangerous’ cannot therefore be seen as justified. The strength of the label ‘dangerous dog’ seems to rule out policies that follow the facts and there is more treating of symptoms than causes. [From the Author]