16S–23S rRNA Intergenic Spacer Region Variability in the Genus Frankia

16S–23S rRNA internally transcribed spacer (ITS) sequences from 53 Frankia strains were sequenced and sized from polymerase chain reaction amplification products and compiled with 14 selected 16S–23S ITS sequences from public database. Frankia genomes included two to three ITS copies lacking length polymorphism except for nine strains. No tRNA gene was encountered in this region. Frankia strains exhibited various lengths (369 to 452 nt) and a wide range of sequence similarity (35–100%) in the ITS region. The average pairwise distance varied from 0.368 (clusters 1 and 2) to 0.964 (clusters 3 and 4) and was 0.397, 0.138, 0.129, and 0.016, respectively, for cluster 4 (saprophytic non-infective/non-effective), clusters 1 and 3 (facultative symbiotic), and cluster 2 (obligate symbiotic). This suggests a gradual erosion of Frankia diversity concomitantly with a shift from saprophytic non-infective/non-effective to facultative and symbiotic lifestyle. Comparative sequence analyses of the 16S–23S rRNA intergenic spacer region of Frankia strains are not useful to assign them to their respective cluster or host infection group. Accurate assignment required the inclusion of the adjacent 16S and 23S rRNA gene fragments.     

Perk Ablation Ameliorates Myelination in S63del-Charcot–Marie–Tooth 1B Neuropathy

In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot–Marie–Tooth disease type 1B (CMT1B)–S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment: Perk haploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/− compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition, Perk deficiency in other cells may contribute to demyelination in a non–Schwann-cell autonomous manner.     

Universal and domain-specific sequences in 23S–28S ribosomal RNA identified by computational phylogenetics

Comparative analysis of ribosomal RNA (rRNA) sequences has elucidated phylogenetic relationships. However, this powerful approach has not been fully exploited to address ribosome function. Here we identify stretches of evolutionarily conserved sequences, which correspond with regions of high functional importance. For this, we developed a structurally aligned database, FLORA (full-length organismal rRNA alignment) to identify highly conserved nucleotide elements (CNEs) in 23S–28S rRNA from each phylogenetic domain (Eukarya, Bacteria, and Archaea). Universal CNEs (uCNEs) are conserved in sequence and structural position in all three domains. Those in regions known to be essential for translation validate our approach. Importantly, some uCNEs reside in areas of unknown function, thus identifying novel sequences of likely great importance. In contrast to uCNEs, domain-specific CNEs (dsCNEs) are conserved in just one phylogenetic domain. This is the first report of conserved sequence elements in rRNA that are domain-specific; they are largely a eukaryotic phenomenon. The locations of the eukaryotic dsCNEs within the structure of the ribosome suggest they may function in nascent polypeptide transit through the ribosome tunnel and in tRNA exit from the ribosome. Our findings provide insights and a resource for ribosome function studies.     

Preference and Performance in Plant–Herbivore Interactions across Latitude–A Study in U.S. Atlantic Salt Marshes

High-latitude plants are often more palatable to herbivores than low-latitude conspecifics. Does increased plant palatability lead to better herbivore performance? Our field and laboratory work investigated (A) whether high-latitude plants have traits indicating that they should be higher-quality foods for herbivores; (B) whether geographic differences in plant quality are more important than local adaptation of herbivores. We studied 3 plant species and 6 invertebrate herbivores in U.S. Atlantic Coast. Past studies had shown high-latitude individuals of these plants are more palatable than low-latitude conspecifics. We documented plant traits and herbivore performance (body size) in the field across latitude. We collected individuals from different latitudes for factorial (plant region x herbivore region) laboratory experiments, examining how herbivore performance was affected by plant region, herbivore region, and their interaction (i.e., local adaptation). Field surveys suggested high-latitude plants were likely of higher quality to herbivores. Leaf nitrogen content in all plant species increased toward high latitudes, consistent with lower leaf C/N and higher leaf chlorophyll content at high latitudes. Furthermore, leaf toughness decreased toward higher latitudes in 1 species. The body size of 4 herbivore species increased with latitude, consistent with high-latitude leaves being of higher quality, while 2 grasshopper species showed the opposite pattern, likely due to life-history constraints. In the laboratory, high-latitude plants supported better performance in 4 herbivore species (marginal in the 5th). The geographic region where herbivores were collected affected herbivore performance in all 6 species; however, the pattern was mixed, indicating a lack of local adaptation by herbivores to plants from their own geographic region. Our results suggest that more-palatable plants at high latitudes support better herbivore growth. Given that geographic origin of either plants or herbivores can affect herbivore performance, the nature of plant-herbivore interactions is likely to change if climate change “reshuffles” plant and herbivore populations across latitude.     

Glutathione-complexed [2Fe-2S] clusters function in Fe–S cluster storage and trafficking

Glutathione-coordinated [2Fe-2S] complex is a non-protein-bound [2Fe-2S] cluster that is capable of reconstituting the human iron-sulfur cluster scaffold protein IscU. This complex demonstrates physiologically relevant solution chemistry and is a viable substrate for iron-sulfur cluster transport by Atm1p exporter protein. Herein, we report on some of the possible functional and physiological roles for this novel [2Fe-2S](GS₄) complex in iron-sulfur cluster biosynthesis and quantitatively characterize its role in the broader network of Fe–S cluster transfer reactions. UV–vis and circular dichroism spectroscopy have been used in kinetic studies to determine second-order rate constants for [2Fe-2S] cluster transfer from [2Fe-2S](GS₄) complex to acceptor proteins, such as human IscU, Schizosaccharomyces pombe Isa1, human and yeast glutaredoxins (human Grx2 and Saccharomyces cerevisiae Grx3), and human ferredoxins. Second-order rate constants for cluster extraction from these holo proteins were also determined by varying the concentration of glutathione, and a likely common mechanism for cluster uptake was determined by kinetic analysis. The results indicate that the [2Fe-2S](GS₄) complex is stable under physiological conditions, and demonstrates reversible cluster exchange with a wide range of Fe–S cluster proteins, thereby supporting a possible physiological role for such centers.     

Ribosomal protein S19 and S24 insufficiency cause distinct cell cycle defects in Diamond–Blackfan anemia

Diamond–Blackfan anemia (DBA) is a severe congenital anemia characterized by a specific decrease of erythroid precursors. The disease is also associated with growth retardation, congenital malformations, a predisposition for malignant disease and heterozygous mutations in either of the ribosomal protein (RP) genes RPS7, RPS17, RPS19, RPS24, RPL5, RPL11 and RPL35a. We show herein that primary fibroblasts from DBA patients with truncating mutations in RPS19 or in RPS24 have a marked reduction in proliferative capacity. Mutant fibroblasts are associated with extended cell cycles and normal levels of p53 when compared to w.t. cells. RPS19 mutant fibroblasts accumulate in the G1 phase, whereas the RPS24 mutant cells show an altered progression in the S phase resulting in reduced levels in the G2/M phase. RPS19 deficient cells exhibit reduced levels of Cyclin-E, CDK2 and retinoblastoma (Rb) protein supporting a cell cycle arrest in the G1 phase. In contrast, RPS24 deficient cells show increased levels of the cell cycle inhibitor p21 and a seemingly opposing increase in Cyclin-E, CDK4 and CDK6. In combination, our results show that RPS19 and RPS24 insufficient fibroblasts have an impaired growth caused by distinct blockages in the cell cycle. We suggest this proliferative constraint to be an important contributing mechanism for the complex extra-hematological features observed in DBA.     

Exploring nursery sites for oviparous chondrichthyans in the Southwest Atlantic (36°S–41°S)

The aim of this paper was to explore egg-laying areas of oviparous chondrichthyans occurring in the northern part of the Southwest Atlantic Ocean (36°S–41°S) at between 50 and 200 metres depth and the Mar del Plata Canyon (from 200 to 3447?m). A total of 515 capsules were collected corresponding to 10 species. Four species accounted for 87.6% of the total catch: Psammobatis normani, Bathyraja macloviana, Amblyraja doellojuradoi and Bathyraja brachyurops. The remaining corresponded to Schroederichthys bivius, Psammobatis rudis, Zearaja chilensis, Bathyraja albomaculata, Psammobatis lentiginosa and Bathyraja sp. Most hauls were monospecific and relatively few hauls contained four or five species (southern part of the area, in sites located at 75 and 94–105?m depth). No egg capsules were recorded between 1712?m and 3447?m. Highest densities (>3000 capsules/km²) were mainly found between 39°46.2′ and 40°29.9′S from 85 to 105?m and they were also recorded near the Mar del Plata Canyon at 37°59.7′S and at 852?m. The highest value recorded was 12,326 capsules/km² (located at 40°18.9′S and 85.4?m). The highest densities for each of the most abundant species are discussed. The finding of high densities of egg cases near the Argentine shelf-break front indicates that many skate species use this area as a nursery site. The egg-laying areas explored here are the first reported sites of this kind in the Southwest Atlantic Ocean. Recognizing and protecting egg-laying habitats may be important steps to a long-term conservation of oviparous chondrichthyan populations.     

Peptide Thioester Synthesis via an Auxiliary-Mediated N–S Acyl Shift Reaction in Solution

The 4,5-dimethoxy-2-mercaptobenzyl (Dmmb) group attached to a main chain amide in a peptide is easily transformed into an S-peptide via an intramolecular N–S acyl shift reaction under acidic conditions, and the S-peptide produces a peptide thioester through an intermolecular thiol–thioester exchange reaction. In order to develop a method for efficiently preparing peptide thioesters based on the N–S acyl shift reaction, the factors involved in this process were analyzed in detail. The general features of the transformation at the Dmmb group attached amide bond in a trifluoroacetic acid (TFA) solution and the generation of a peptide thioester were examined by ¹³C-NMR spectral measurements, reversed-phase (RP) HPLC analyses, mass measurements, and amino acid analyses. The methoxy group of the Dmmb group was not essential for the N–S acyl shift reaction, but played a role in stabilizing the thioester form. The addition of water to the TFA solution accelerated the N–S acyl shift reaction mediated by the Dmmb group and also suppressed the acid-catalyzed cleavage of the Dmmb group. A peptide thioester was produced from the S-peptide via an intermolecular thiol–thioester exchange reaction with minimal epimerization of the amino acid residue that constituted the thioester bond. Undesirable side reactions, such as the hydrolysis of the thioester bond and an S–N acyl shift reaction occurred during the synthetic process, which is a subject of further investigation.     

Autometallographic tracing of Hg–S quantum dots in frogs exposed to inorganic mercury

The histochemical distribution of mercury in the kidneys and gut of frogs (Rana ridibunda) exposed to inorganic mercury was analyzed with autometallography (AMG). It was found that most mercury in the kidneys accumulated in the proximal convoluted tubules as Hg–S nanocrystal, while control animals were totally void of AMG grains. In the gut the highest concentration of mercury was observed in the large intestine. The AMG grains were primarily located in the apical part of the absorptive cells, although rather high concentrations of silver enhanced mercury quantum dots were also detected in a special cell type of gut epithelium and the glycocalyx. A certain amount of AMG grains were detected in the lumen of the gut. We hypothesize that this pool of quantum dots results from sloughed off epithelial cells and macrophages. Such still intact cells and red blood cells containing AMG grains were also found in the lumen of the gut.     

Characteristics and application of S1–P1 nucleases in biotechnology and medicine

3′–nucleases/nucleotidases of the S1–P1 family (EC 3.1.30.1) are single–strand–specific or non-specific zinc–dependent phosphoesterases present in plants, fungi, protozoan parasites, and in some bacteria. They participate in a wide variety of biological processes and their current biotechnological applications rely on their single–strand preference, nucleotide non-specificity, a broad range of catalytic conditions and high stability. We summarize the present and potential utilization of these enzymes in biotechnology and medicine in the context of their biochemical and structure–function properties. Explanation of unanswered questions for bacterial and trypanosomatid representatives could facilitate development of emerging applications in medicine.     

S1–S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation

The movement of positively charged S4 segments through the electric field drives the voltage-dependent gating of ion channels. Studies of prokaryotic sodium channels provide a mechanistic view of activation facilitated by electrostatic interactions of negatively charged residues in S1 and S2 segments, with positive counterparts in the S4 segment. In mammalian sodium channels, S4 segments promote domain-specific functions that include activation and several forms of inactivation. We tested the idea that S1–S3 countercharges regulate eukaryotic sodium channel functions, including fast inactivation. Using structural data provided by bacterial channels, we constructed homology models of the S1–S4 voltage sensor module (VSM) for each domain of the mammalian skeletal muscle sodium channel hNa_V1.4. These show that side chains of putative countercharges in hNa_V1.4 are oriented toward the positive charge complement of S4. We used mutagenesis to define the roles of conserved residues in the extracellular negative charge cluster (ENC), hydrophobic charge region (HCR), and intracellular negative charge cluster (INC). Activation was inhibited with charge-reversing VSM mutations in domains I–III. Charge reversal of ENC residues in domains III (E1051R, D1069K) and IV (E1373K, N1389K) destabilized fast inactivation by decreasing its probability, slowing entry, and accelerating recovery. Several INC mutations increased inactivation from closed states and slowed recovery. Our results extend the functional characterization of VSM countercharges to fast inactivation, and support the premise that these residues play a critical role in domain-specific gating transitions for a mammalian sodium channel.     

Halogen–water–hydrogen bridges in biomolecules

The importance of water in biological systems has long been recognized in chemistry and biology communities. In this article we describe a new manner by which water affects biomolecular behaviors, called halogen–water–hydrogen bridge (XWH bridge), that is, one hydrogen bonding (H-bonding) in water-mediated H-bond bridge is replaced by halogen bonding (X-bonding). Although behaving similarly to water-mediated H-bond motif, the XWH bridge usually stands in multifurcated forms and possesses stronger directionality. Quantum mechanical analysis on several model and real systems reveals that the XWH bridges are more thermodynamically stable than other water-involved interactions, and this stability is further enhanced by the cooperation of X-bonding and H-bonding. Crystal structure survey clearly demonstrates the significance of XWH bridges in stabilization of biomolecular conformations and in mediation of protein–protein, protein–nucleic acid, and receptor–ligand recognition and binding. These findings shed light into the potential value of XWH bridges in drug design and biological engineering.     

Infective Endocarditis in the U.S., 1998–2009: A Nationwide Study

Background

Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings

Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients with intra-cardiac devices rose from 13.3% to 18.9%, while the share with drug use and/or HIV fell. Mortality remained stable at about 14.5%, as did cardiac valve replacement (9.6%). Other serious complications increased; 13.3% of patients in 2009 suffered a stroke or CNS infection, and 5.5% suffered myocardial infarction. Amongst cases with identified pathogens, Staphylococcus aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were MRSA. Streptococci were mentioned in 24.7% of cases, gram-negatives in 5.6% and Candida species in 1.0%. We detected no inflection in hospitalization rates after changes in prophylaxis recommendations in 2007. Mean age rose from 58.6 to 60.8 years; elderly patients suffered higher rates of myocardial infarction and death, but slightly lower rates of Staphylococcus aureus infections and neurologic complications. Our study relied on clinically diagnosed cases of endocarditis that may not meet strict criteria. Moreover, since some patients are discharged and readmitted during a single episode of endocarditis, our hospitalization figures probably slightly overstate the true incidence of this illness.

Conclusions

Endocarditis is more common in the U.S. than previously believed, and is steadily increasing. Preventive efforts should focus on device-associated and health-care-associated infections.     

Superoxide-Driven Aconitase FE–S Center Cycling

O^- ₂ produced by the autoxidation of respiratory chain electron carriers, and other cellular reductants, inactivates bacterial and mammalian iron-sulfur-containing (de)hydratases including the citric acid cycle enzyme aconitase. Release of the solvent-exposed iron atom and oxidation of the [4Fe-4S]²⁺ cluster accompanies loss of catalytic activity. Rapid reactivation is achieved by iron-sulfur cluster reduction and Fe²⁺ insertion. Inactivation-reactivation is a dynamic and cyclical process which modulates aconitase and (de)hydratase activities in Escherichia coli and mammalian cells. The balance of inactive and active aconitase provides a sensitive measure of the changes in steady-statO^- ₂ levels occuring in living cells and mitochondria under stress conditions. Aconitases are also inactivated by other oxidants including O₂, H₂O₂, NO^., and ONOO^– which are associated with inflammation, hyperoxia and other pathophysiological conditions. Loss of aconitase activity during oxidant stress may impair energy production, and the liberation of reactive iron may further enhance oxidative damage. Iron-sulfur center cycling may also serve adaptive functions by modulating gene expression or by signaling metabolic quiescence.     

U.S. National Institutes of Health Core Consolidation–Investing in Greater Efficiency

The U.S. National Institutes of Health (NIH) invests substantial resources in core research facilities (cores) that support research by providing advanced technologies and scientific and technical expertise as a shared resource. In 2010, the NIH issued an initiative to consolidate multiple core facilities into a single, more efficient core. Twenty-six institutions were awarded supplements to consolidate a number of similar core facilities. Although this approach may not work for all core settings, this effort resulted in consolidated cores that were more efficient and of greater benefit to investigators. The improvements in core operations resulted in both increased services and more core users through installation of advanced instrumentation, access to higher levels of management expertise; integration of information management and data systems; and consolidation of billing; purchasing, scheduling, and tracking services. Cost recovery to support core operations also benefitted from the consolidation effort, in some cases severalfold. In conclusion, this program of core consolidation resulted in improvements in the effective operation of core facilities, benefiting both investigators and their supporting institutions.     

Sesbania herbacea–Rhizobium huautlense Nodulation in Flooded Soils and Comparative Characterization of S. herbacea-Nodulating Rhizobia in Different Environments

Abstract The nodulation of S. herbacea was compared under flooded and non-flooded conditions in two different soils. One soil was from a flooded field in Sierra de Huautla, the native habitat of this legume, while the other soil was from a well-drained field in Cuernavaca, where rhizobia were found to nodulate the introduced S. herbacea plants. Nodulation of the plants was completely eliminated by flooding in the Cuernavaca soil, whereas nodules were obtained in the same soil under non-flooded conditions. In contrast, nodules were formed in Huautla soil under both flooded and non-flooded conditions. Most isolates, except isolate HS2, from Huautla soil and water were identified as R. huautlense by colony morphology, growth rate, PCR-RFLP of 16S rRNA genes, MLEE, cellular plasmid contents, and RFLP of nifH and nodDAB genes. Isolate HS2 was identified as Mesorhizobium sp. Isolates from Cuernavaca soil were different from R. huautlense in many aspects and were classified into five rDNA types within the genera Mesorhizobium, Rhizobium, and Sinorhizobium by PCR-RFLP of 16S rRNA genes. R. huautlense is a water Rhizobium species. Growth by denitrification under oxygen limitation or with ethanol was observed for R. huautlense bacteria but not for the isolates from Cuernavaca. In an interstrain nodulation competitive assay under both flooded and non-flooded conditions, R. huautlense strain S02 completely inhibited the nodulation of Mesorhizobium sp. Sn2, an isolate from Cuernavaca. From these results, we conclude that R. huautlense has the unique ability to nodulate S. herbacea not only in flooded soils, but in non-flooded soils as well. Received: 16 August 1999; Accepted: 28 December 1999; Online Publication: 13 June 2000     

Rapamycin-enhanced mitomycin C-induced apoptotic death is mediated through the S6K1–Bad–Bak pathway in peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) is the most common secondary cancerous disease, and more effective novel regimens are needed. In this study, we identified a novel combination treatment for PC, chemotherapeutic agent mitomycin C in combination with mTOR (mammalian target of rapamycin) inhibitor rapamycin. We observed that the combination of mitomycin C and rapamycin induced synergistic cytotoxicity and apoptosis, which was mediated through an increase in caspase activation. The combination of mitomycin C and rapamycin inactivated p70 S6 ribosomal kinase (S6K1) and dephosphorylated Bad, leading to dissociation of Bcl-xL from Bak, which resulted in Bak oligomerization, mitochondria dysfunction and cytochrome c release. PF-4708671, a S6K1-specific inhibitor, enhanced the combination treatment-induced apoptosis, whereas S6K1 E389 DeltaCT-HA (S6K1 active form) dramatically decreased the induction of apoptosis. In addition, the combination treatment significantly inhibited LS174T intraperitoneal tumor growth in vivo. This study provides a preclinical rationale for apoptosis induction linked with the mTOR pathway through a combination of chemotherapeutic agents and mTOR inhibitor, and will support this combinatorial strategy to PC patients.Peritoneal carcinomatosis (PC) is the most common secondary cancerous disease to affect the peritoneal cavity following colorectal cancer, appendiceal cancer, ovarian cancer, gastric cancer, or diffuse malignant peritoneal mesothelioma, and is regarded as a lethal condition having poor prognosis with a median survival of ∼6 months.^{1, 2} Systemic chemotherapy prolongs survival in PC patients, but is less effective than for patients with hepatic metastasis; thus, an increasing number of patients are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemoperfusion (HIPEC).³ Nevertheless, more effective novel regimens are still needed to improve the survival of PC patients.Mitomycin C, a potent DNA crosslinker, was used as an anticancer drug and led to pronounced induction of apoptosis, especially through the mitochondrial-dependent pathway.^{4, 5} It has received a great number of preclinical and clinical studies and is mostly widely used for PC.⁶ Combination of cytotoxic drugs, such as mitomycin C with novel biological agents, has achieved improvement in animal models and provides additional survival benefits for patients.^{7, 8, 9}mTOR (mammalian target of rapamycin), a serine/threonine kinase, is ubiquitously involved in cell growth and proliferation. The fact that hyperactivation of mTOR is a common feature of human cancers makes it an attractive target in cancer therapy.¹⁰ It has been reported that some agents inactivate mTOR signaling as an early response prior to the execution of apoptosis.^{11, 12} Recently, it has been found that mTOR can directly control mitochondrial function,¹³ which raises the possibility that targeting mTOR may regulate the apoptotic pathway. Sirolimus, known as rapamycin, an mTOR inhibitor, potently inhibits S6K1 (S6 ribosomal kinase) activity¹⁴ and has been generally well tolerated in clinical trials, often inducing prolonged stable disease or tumor regression, and can be considered as an option for combination with other anticancer agents.^{15, 16}In this study we observed that the combination of chemotherapy agent mitomycin C and mTOR inhibitor rapamycin induced synergistic cytotoxicity and apoptosis in vitro and in vivo. The combination of mitomycin C and rapamycin inactivated S6K1, not Akt, and resulted in dephosphorylation of Bad, which inactivated its pro-apoptotic function, inducing Bak oligomerization and mitochondrial-dependent apoptotic cell death.     

Variation in annual pollen accumulation rates of Fagus along a N–S transect in Europe based on pollen traps

Annual pollen-accumulation rates (PAR) of Fagus (beech) obtained within the framework of the Pollen Monitoring Programme (PMP) were analyzed in pollen traps along a N–S transect from the Baltic Sea to the Black Sea in different European vegetation units. The study regions are situated in the lowlands of northern Poland, the uplands of SE Poland, the Czech Krkono?e Mts, the Czech ?umava Mts, the Swiss Jura Mts, the Swiss Alps, the Bulgarian Rila Mts and the Bulgarian Strandzha Mts. Most time series are 10 or 11 years long, some are 5–16 years long. Inter-annual fluctuations in Fagus PAR were analyzed and compared with seed mast years. Years with high Fagus PAR and others with low Fagus PAR occurred most frequently in parallel within each region and often in two neighbouring regions. 2006 was exceptional as it had a very high Fagus sylvatica pollen deposition in all study regions and it was also a mast year. In Bulgaria, the trend in the 5 years of Fagus orientalis PAR in the Strandzha Mts differed from that of F. sylvatica PAR in the Rila Mts. Aiming at establishing the relationship between average Fagus PAR and tree cover, differences in Fagus PAR (averaged per pollen trap) were related in each region to the proportion of beech trees in the vegetation within 2 km of the pollen traps, the distance to the nearest pollinating Fagus tree, regional or local presence of beech forests, the degree of landscape openness, and the size of forest opening in which a trap is situated. Average Fagus PAR was found to track the regional abundance of beech trees in the vegetation, not the distance of the nearest Fagus tree. Regional occurrence of beech-dominated forests was reflected by a Fagus PAR of ca. 1,400 grains cm^?2 year^?1, local abundance very close to pollen traps by ca. 2,400 grains, small patches of forest with admixture of Fagus by ca. 170–220 grains, and scarcity or absence of Fagus by ca. 40 grains or less.     

Geographic variations in cancer incidence and mortality in the State of São Paulo,Brazil 2001–17

BackgroundCancer is a leading cause of morbidity and mortality in Brazil and the burden is rising. To better inform tailored cancer actions, we compare incidence and mortality profiles according to small areas in the capital and northeast region of the State of São Paulo for the leading cancer types.MethodsNew cancer cases were obtained from cancer registries covering the department of Barretos (2003–2017) and the municipality of São Paulo (2001–2015). Cancer deaths for the same period were obtained from a Brazilian public government database. Age-standardized rates per 100,000 persons-years by cancer and sex are presented as thematic maps, by municipality for Barretos region, and by district for São Paulo.ResultsProstate and breast cancer were the leading forms of cancer incidence in Barretos, with lung cancer leading in terms of cancer mortality in both regions. The highest incidence and mortality rates were seen in municipalities from the northeast of Barretos region in both sexes, while elevated incidence rates were mainly found in São Paulo districts with high and very high socioeconomic status (SES), with mortality rates more dispersed. Breast cancer incidence rates in São Paulo were 30 % higher than Barretos, notably in high and very high SES districts, while corresponding rates of cervical cancer conveyed the opposite profile, with elevated rates in low and medium SES districts.ConclusionsThere is substantial diversity in the cancer profiles in the two regions, by cancer type and sex, with a clear relation between the cancer incidence and mortality patterns observed at the district level and corresponding SES in the capital.