Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

Limitation of seedling growth by potassium and magnesium supply for two ectomycorrhizal tree species of a Central African rain forest and its implication for their recruitment

In the ectomycorrhizal caesalpiniaceous groves of southern Korup National Park, the dominant tree species, Microberlinia bisulcata, displays very poor in situ recruitment compared with its codominant, Tetraberlinia bifoliolata. The reported ex situ experiment tested whether availabilities of soil potassium and magnesium play a role. Seedlings of the two species received applications of K and Mg fertilizer in potted native soil in a local shade house, and their responses in terms of growth and nutrient concentrations were recorded over 2 years. Amended soil concentrations were also determined. Microberlinia responded strongly and positively in its growth to Mg, but less to K; Tetraberlinia responded weakly to both. Added Mg led to strongly increased Mg concentration for Microberlinia while added K changed that concentration only slightly; Tetraberlinia strongly increased its concentration of K with added K, but only somewhat its Mg concentration with added Mg. Additions of Mg and K had small but important antagonistic effects. Microberlinia is Mg-demanding and apparently Mg-limited in Korup soil; Tetraberlinia, whilst K-demanding, appeared not to be K-limited (for growth). Added K enhanced plant P concentrations of both species. Extra applied Mg may also be alleviating soil aluminum toxicity, and hence improving growth indirectly and especially to the benefit of Microberlinia. Mg appears to be essential for Microberlinia seedling growth and its low soil availability in grove soils at Korup may be an important contributing factor to its poor recruitment. Microberlinia is highly shade-intolerant and strongly light-responding, whilst Tetraberlinia is more shade-tolerant and moderately light-responding, which affords an interesting contrast with respect to their differing responses to Mg supply. The study revealed novel aspects of functional traits and likely niche-partitioning among ectomycorrhizal caesalps in African rain forests. Identifying the direct and interacting indirect effects of essential elements on tropical tree seedling growth presents a considerable challenge due the complex nexus of causes involved.

A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes.

Discovery of novel drug targets may lead to improved treatment of trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary sequences of the 2 proteins--protein encoded by gene Tb927.1.4450 (TbK1) and protein encoded by gene Tb927.9.4820 (TbK2)--indicate that both belong to the family of putative, Ca(2+)-activated potassium channels. The proteins were expressed in Xenopus laevis oocytes and their functions investigated by use of electrophysiological techniques. Only combined expression of TbK1 and TbK2 results in the formation of sizeable currents, indicating that these proteins probably assemble into a heteromeric ion channel. The current mediated by this channel shows little time and voltage dependence and displays a permeability ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits this channel with a half-maximal inhibitory concentration (IC50) of 98 ± 15 μM. The membrane potential of trypanosomes was measured with a fluorescent dye. Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium conductance in the plasma membrane of BSF. Thus, this heteromeric potassium channel is involved in the modulation of the plasma membrane potential and represents a novel drug target in T. brucei.

CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility.

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways.

Kentucky Bluegrass Response to Potassium and Nitrogen Fertilization

The response of Kentucky bluegrass (Poa pratensis L.) to potassium (K) fertilization has been inconsistent. The objective of this research was to determine the effects of K fertilization across varying nitrogen (N) rates and clipping management on Kentucky bluegrass clipping yields, quality, tissue K concentrations, apparent N recovery, and N use efficiency. A 2 x 4 x 4 factorial was arranged in a splitplot design and repeated across two years. Main plots were clipping treatments (returned vs. removed) and subplots were N rates (0, 98, 196, and 294 kg ha(-1) yr(-1)) in combination with K rates (0, 81, 162, and 243 kg ha(-1) yr(-1)). There was no positive effect of K on clipping yields and quality even though soil extractable K levels tested low. Higher K rates, however, increased N recovery and use efficiency for all but the highest N rate. Tissue K response to K fertilization was nonlinear. Yield and quality responses were not correlated to tissue K concentration. Nonexchangeable K levels were high in the native soil, and may have provided an additional source of K for bluegrass. The results suggest that extractable K values alone may not adequately predict available K to Kentucky bluegrass in this sandy loam soil.

Broadcast and Band Phosphorus and Potassium Placement for Corn and Soybean Managed with Till or No Till

No-till minimizes the incorporation of crop residue and fertilizer with soil; resulting in wetter, colder soils and the accumulation of organic matter, phosphorus (P), and potassium (K) near the soil surface. Banding of P and Kcould be more effective than broadcast fertilization by counteracting stratification, applying nutrients in the root zone (starter effect), and minimizing reactions with the soil that may reduce their availability to plants. Therefore, a long-term study was established in 1994 to evaluate P and K fertilizer rates and placement methods for grain yield of corn and soybean managed with no-till and chiselplow/disk tillage.

Long-term Evaluation of Hybrid, Nitrogen, and Potassium Interactions in Continuous Corn

A long-term experiment was established in 2009 to study continuous corn responses to potassium (K), nitrogen (N), and hybrid rootworm resistance. Previous research suggested a need for this study. A long-term trial conducted until 2001 at the ISU Northern Research Farm showed that the maximum corn yield level and the N rate that maximized yield was higher when K was optimal or greater. In contrast, the relative yield response to N and the N rate that maximized yield were similar for soil-test phosphorus (P) levels ranging from very low to very high. Other studies have shown that rootworm resistance often increases yield compared with untreated susceptible hybrids. Also, that rootworm resistance does not consistently affect the K rate that maximizes yield, but increases K removal because of the higher yield levels. Therefore, this new study evaluates possible interactions between rootworm resistance and N and K fertilization in corn.

Phosphorus and Potassium Rates and Placement Methods for Corn and Soybean Managed with No-till or Tillage

No-till management for corn and soybean results in little or no incorporation of crop residues and fertilizer with soil. Subsurface banding phosphorus (P) and potassium (K) fertilizers with planter attachments could be more effective than broadcast fertilization, because in no-till with broadcast fertilizer, both nutrients accumulate at or near the soil surface. A long-term study was initiated in 1994 at the ISU Northwest Research Farm to evaluate P and K fertilizer placement for corn and soybean managed with no-till and chiselplow tillage.

Placement Methods of Phosphorus and Potassium for Corn and Soybean Managed with No-till and Chisel-plow/Disk Tillage

No-till management limits the incorporation of crop residue and fertilizer with soil resulting in wetter, colder soils and the accumulation of organic matter, phosphorus (P), and potassium (K) near the soil surface. Banding of P and K could be more effective than broadcast fertilization by counteracting stratification, applying nutrients in the root zone (starter effect), and minimizing reactions with the soil that may reduce their availability to plants. Therefore, this long-term study was established in 1994 to evaluate P and K fertilizer placement methods and grain yield of corn-soybean rotations managed with notill and chisel-plow/disk tillage.

(Table 1) Potassium, radiogenic Argon 40 and dated age for DSDP Hole 94-608 sediments

K-Ar dates were obtained for three pillow basalt samples recovered from Site 608 (Samples 608-58-1, 103-109 cm; 608-59-1, 3-7 cm; 608-59-1, 48-53 cm). Reliable K-Ar dates cannot be routinely obtained for deep-sea igneous rocks, because they may be subject to inaccuracies related to seawater alteration (Seidemann, 1977, doi:10.1130/0016-7606(1977)88<1660:EOSAOK>2.0.CO;2) and/or the presence of excess radiogenic 40Ar (Dalrymple and Moore, 1968, doi:10.1126/science.161.3846.1132; Dymond, 1970, doi:10.1130/0016-7606(1970)81[1229:EAISBP]2.0.CO;2). Thus, the possibility that the samples dated in this study were subject to these sources of inaccuracy must be evaluated.

Potassium and argon concentrations and age determination of ODP Site 125-782 and 125-786

K-Ar whole-rock ages have been obtained for 30 samples from Sites 782 and 786, Ocean Drilling Program Leg 125 in the Izu-Bonin (Ogasawara) forearc region. They form a trimodal spread of ages between 9 Ma and 44 Ma and are, with a few exceptions, consistent with the inferred lithostratigraphy. The ages have been interpreted in terms of at least two distinct episodes of magmatic and/or hydrothermal activity. A group of ten samples, including the lava flows, gave an isochron age of 41.3 ± 0.5 Ma (middle-late Eocene). This is thought to represent the age of the principal magmatic development of the volcanic forearc basement, and is comparable to published ages on equivalent rocks from other parts of the forearc basement high (e.g., the Ogasawara Islands). It may be significant that this age is slightly younger than the timing of major plate reorganization in the Western Pacific at about 43 Ma. This was followed by a minor episode of intrusive magmatism at 34.6 ± 0.7 Ma (early Oligocene) which appears to have reset the ages of some of the earlier units. This event probably corresponds to the initiation of rifting of the "proto-arc" to form the Parece Vela Basin. Boninitic samples were erupted during both episodes of magmatism, the earlier being of low-Ca boninite type and the later being of medium- and high-Ca types. It is also possible that a third episode of intrusive magmatism affected the Izu-Bonin forearc region at both Sites 782 and 786 at about 17 Ma. This would be consistent with magmatic activity elsewhere in the region during the Miocene, associated with the end of active spreading in the Parece Vela Basin and the start of arc activity in the West Mariana Ridge.