The genetic diversity of ampeloviruses in Australian pineapples and their association with mealybug wilt disease

Pineapple mealybug wilt-associated virus 1 (PMWaV-1), 2 (PMWaV-2) and -3 (PMWaV-3) have been detected in Australian commercial pineapple crops, along with a previously undescribed ampelovirus, for which the name Pineapple mealybug wilt-associated virus 5 (PMWaV-5) is proposed. Partial sequences extending from open reading frame 1b through to the heat shock protein homologue were obtained for PMWaV-1, -3 and -5. Phylogenetic analyses of selected regions of these sequences indicated that PMWaV-5 is a distinct species and most closely related to PMWaV-1. The amino acid sequence variation observed in the RNA-dependent RNA polymerase region of PMWaV-1 isolates was 95.8–98.4% and of PMWaV-3 isolates was 92.2–99.5%. In surveys of mealybug wilt disease (MWD) affected crops, none of the four viruses was clearly associated with the disease at all survey sites. A statistically significant association (P < 0.001) between the presence of PMWaV-2 and symptoms was observed at one survey site (site 3), but the virus was at a low incidence at the remaining three survey sites. By contrast, although PMWaV-1 and -3 were equally distributed between symptomless and MWD-affected plants at site 3, there was a statistically significant (P < 0.001) association between each of these two viruses and MWD at sites 1 and 4. At site 2, there was a statistically significant (P < 0.001) association only between PMWaV-3 and MWD. PMWaV-1 was the most commonly found of the four viruses and conversely PMWaV-5 was only occasionally found. Australian isolates of PMWaV-1, -2 and -3 were transmitted by the mealybug species Dysmicoccus brevipes.

Split-Freedom And Mvd-Intersection - A New Characterization Of Multivalued Dependencies Having Conflict-Free Covers

Sets of multivalued dependencies (MVDs) having conflict-free covers are important to the theory and design of relational databases [2,12,15,16]. Their desirable properties motivate the problem of testing a set M of MVDs for the existence of a confiict-free cover. In [8] Goodman and Tay have proposed an approach based on the possible equivalence of M to a single (acyclic) join dependency (JD). We remark that their characterization does not lend an insight into the nature of such sets of MVDs. Here, we use notions that are intrinsic to MVDs to develop a new characterization. Our approach proceeds in two stages. In the first stage, we use the notion of “split-free” sets of MVDs and obtain a characterization of sets M of MVDs having split-free covers. In the second, we use the notion of “intersection” of MVDs to arrive at a necessary and sufficient condition for a split-free set of MVDs to be conflict-free. Based on our characterizations, we also give polynomial-time algorithms for testing whether M has split-free and conflict-free covers. The highlight of our approach is the clear insight it provides into the nature of sets of MVDs having conflict-free covers. Less emphasis is given in this paper to the actual efficiency of the algorthms. Finally, as a bonus, we derive a desirable property of split-free sets of MVDs,thereby showing that they are interesting in their own right.

Studio portrait of Elfriede Maria Roth; Cambridge, Massachusetts Portraits; Children

When Bruno Roth arrived in the United States in 1939 he opened a photo studio. He used this photograph for advertising

Portrait of Else Walter Roth Portraits; Women

Else Walter Roth, born 11 September 1894. Wife of Bruno Roth and mother of Christine Roth-Schurtman

Portrait of Dr. Elisabeth Cobb Portraits; Women

Dr. Elisabeth Cobb and her husband Dr. Cobb provided the affidavit allowing Bruno Roth to come to the United States. They were both doctors and Quakers and lived in Cambridge, Massachusetts

Portrait of Dr. Cobb Portraits; Men

Dr. Cobb and his wife Dr. Elisabeth Cobb provided the affidavit allowing Bruno Roth to come to the United States. They were both doctors and Quakers and lived in Cambridge, Massachusetts

Portrait of Dr. Cobb Portraits; Men

Dr. Cobb and his wife Dr. Elisabeth Cobb provided the affidavit allowing Bruno Roth to come to the United States. They were both doctors and Quakers and lived in Cambridge, Massachusetts

Amber teething necklaces: Is there any basis to their use in teething infants?

Introduction. Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound said to have analgesic and anti-inflammatory properties), which is then absorbed through the skin. Aims. To investigate whether succinic acid is contained in Baltic amber teething necklaces purchased in Australia, whether it can be released from the beads, and whether it has anti-inflammatory activity. Methods. Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol. Anti-inflammatory activity of succinic acid was compared with ibuprofen, paracetamol and hydrocortisone in vitro using THP-1 human macrophages stimulated with LPS. Secretion of the cytokines IL-1a, IL-1b, IL-8 and TNF-α were determined by ELISA. Results. Each necklace (33 beads in length) contained 19.17 ± 4.89 mg of succinic acid (mean ± se). Over a 6-month period, no succinic acid was detected in PBS. While 0.13 ± 0.09 mg of succinic acid per necklace was released in octanol, this was due to only one replicate of amber beads which had fragmented into shards free-floating in the solvent. Succinic acid had no effect on cytokine secretion unless extremely high concentrations were used and changes were likely to be associated with cell apoptosis and death. Discussion. No evidence for anti-inflammatory activity was found in the cytokines studied. It is possible that succinic acid could exert an effect via some other mechanism, but while the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

Defects in tricarboxylic acid cycle enzymes Fumarate hydratase and Succinate dehydrogenase in cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a recently characterized cancer syndrome which predisposes to cutaneous and uterine leiomyomas as well as renal cell carcinoma (RCC). Uterine leiomyosarcoma (ULMS) has also been observed in certain Finnish HLRCC families. The predisposing gene for this syndrome, fumarate hydratase (FH), was identified in 2002. The well-known function of FH is in the tricarboxylic acid cycle (TCAC) in the energy metabolism of cells. As FH is a novel cancer gene, the role of FH mutations in tumours is in general unknown. Similarly, the mechanisms through which defective FH is associated with tumourigenesis are unclear. The loss of a wild type allele has been observed in virtually all HLRCC patients tumours and the FH enzyme activities are either totally lost or remarkably reduced in the tissues of mutation carrier patients. Therefore, FH is assumed to function as a tumour suppressor. Mutations in genes encoding subunits of other TCAC enzyme SDH have also been reported recently in tumours: mutations in SDHB, SDHC, and SDHD genes predispose to paraganglioma and pheochromocytoma. In the present study, mutations in the SDHB gene were observed to predispose to RCC. This was the first time that mutations in SDHB have been detected in extra-paraganglial tumours. Two different SDHB mutations were observed in two unrelated families. In the first family, the index patient was diagnosed with RCC at the age of 24 years. Additionally, his mother with a paraganglioma (PGL) of the heart and his maternal uncle with lung cancer were both carriers of the mutation. The RCC of the index patient and the PGL of his mother showed LOH. In the other family, an SDHB mutation was detected in two siblings who were both diagnosed with RCC at the ages of 24 and 26 years. Both of the siblings also suffered PGL. All these tumours showed LOH. Therefore, we concluded that mutations in SDHB predispose also for RCC in certain families. Several tumour types were analysed for FH mutations to define the role of FH mutations in these tumour types. In addition, patients with a putative cancer phenotype were analysed to identify new HLRCC families. Three FH variants were detected, of which two were novel. One of the variants was observed in a patient diagnosed with ULMS at the age of 41 years. However, LOH was not detected in the tumour tissue. The FH enzyme activity of the mutated protein was clearly reduced, being 43% of the activity of the normal protein. Together with the results from an earlier study we calculated that the prevalence of FH mutations in Finnish non-syndromic ULMS is around 2.4%. Therefore, FH mutations seem to have a minor role in the pathogenesis on non-syndromic ULMS. Two other germline variants were detected in a novel tumour type, ovarian mucinous cystadenoma. However, tumour tissues of the patients were not available for LOH studies and therefore LOH status remained unclear. Therefore, it is possible that FH mutations predispose also for ovarian tumours but further studies are needed to verify this result. A novel variant form of the FH gene (FHv) was identified and characterized in more detail. FHv contains an alternative first exon (1b), which appeared to function as 5 UTR sequence. The translation of FHv is initiated in vitro from exons two and three. The localization of FHv is both cytosolic and nuclear, in contrast to the localization of FH in mitochondria. FHv is expressed at low levels in all human tissues. Interestingly, the expression was induced after heat shock treatment and in chronic hypoxia. Therefore, FHv might have a role e.g. in the adaptation to unfavourable growth conditions. However, this remains to be elucidated.

Self-Assembly of Molecular Prisms via Pt-3 Organometallic Acceptors and a Pt-2 Organometallic Clip

The design and two-component [2 + 3] self-assembly of a series of new organometallic molecular prisms (3a-d) are described. Assemblies 3a,b incorporate 4,4',4'-tris[ethynyl-trans-Pt(PEt3)(2)]triphenylamine (1a) containing a Pt-ethynyl functionality as tritopic planar acceptor and organic ``clips'' 2a and 2b, respectively [where 2a = 1,3-bis(3-pyridyl)isophthalic amide; 2b= 1,3-bis(ethynyl-3-pyridyl)benzene]. In a complementary approach all organic tritopic planar donor ligand 2c [2c 4,4',4'-tris(4-pyridylethynyl)triphenylamine] was assembled with all organometallic ``clip'', 1,8-bis[{trans-Pt(PEt3) (2)(NO3)}ethynyl]anthracene (1b), to obtain prism 3c. A organometallic carbon-centered acceptor, 1,1,1- tris[4-{trans-Pt(PEt3)(2)(NO3)}ethynylphenyl]ethane (1c), has been prepared, and its prism derivative (3d) using an organic `clip'' is prepared. Assemblies (3a-d) were characterized by multinuclear NMR spectroscopy, electrospray ionization mass spectroscopy, and elemental analysis. 3a-d showed fluorescence behavior in solution, and quenching of fluorescence intensity (3a,3c-d) was noticed upon addition of TNT (2,4,6-trinitrotoluene), a common constituent of many commercial explosives. A thin film of the assembly 3d made by spin coating of a solution of 3 x 10(-5) M in DMF on it 1 cm(2) quartz plate showed fluorescence response to the vapor of TNT.

Molecular and clinical characteristics of tricarboxylic acid cycle-associated tumors

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare, dominantly inherited tumor predisposition syndrome characterized by benign cutaneous and uterine (ULM) leiomyomas, and sometimes renal cell cancer (RCC). A few cases of uterine leiomyosarcoma (ULMS) have also been reported. Mutations in a nuclear gene encoding fumarate hydratase (FH), an enzyme of the mitochondrial tricarboxylic acid cycle (TCA cycle), underlie HLRCC. As a recessive condition, germline mutations in FH predispose to a neurological defect, FH deficiency (FHD). Hereditary paragangliomatosis (HPGL) is a dominant disorder associated with paragangliomas and pheochromocytomas. Inherited mutations in three genes encoding subunits of succinate dehydrogenase (SDH), also a TCA cycle enzyme, predispose to HPGL. Both FH and SDH seem to act as tumor suppressors. One of the consequences of the TCA cycle defect is abnormal activation of HIF1 pathway ( pseudohypoxia ) in the HLRCC and HPGL tumors. HIF1 drives transcription of genes encoding e.g. angiogenetic factors which can facilitate tumor growth. Recently hypoxia/HIF1 has been suggested to be one of the causes of genetic instability as well. One of the aims of this study was to broaden the clinical definers of HLRCC. To determine the cancer risk and to identify possible novel tumor types associated with FH mutations eight Finnish HLRCC/FHD families were extensively evaluated. The extension of the pedigrees and the Finnish Cancer Registry based tumor search yielded genealogical and cancer data of altogether 868 individuals. The standardized incidence ratio-based comparison of HLRCC/FHD family members with general Finnish population revealed 6.5-fold risk for RCC. Moreover, risk for ULMS was highly increased. However, according to the recent and more stringent diagnosis criteria of ULMS many of the HLRCC uterine tumors previously considered malignant are at present diagnosed as atypical or proliferative ULMs (with a low risk of recurrence). Thus, the formation of ULMS (as presently defined) in HLRCC appears to be uncommon. Though increased incidence was not observed, interestingly the genetic analyses suggested possible association of breast and bladder cancer with loss of FH. Moreover, cancer cases were exceptionally detected in an FHD family. Another clinical finding was the conventional (clear cell) type RCC of a young Spanish HLRCC patient. Conventional RCC is distinct from the types previously observed in this syndrome but according to these results, FH mutation may underlie some of young conventional cancer cases. Secondly, the molecular pathway from defective TCA cycle to tumor formation was intended to clarify. Since HLRCC and HPGL tumors display abnormally activated HIF1, the hypothesis on the link between HIF1/hypoxia and genetic instability was of interest to study in HLRCC and HPGL tumor material. HIF1α (a subunit of HIF1) stabilization was confirmed in the majority of the specimens. However, no repression of MSH2, a protein of DNA mismatch repair system, or microsatellite instability (MSI), an indicator of genetic instability, was observed. Accordingly, increased instability seems not to play a role in the tumorigenesis of pseudohypoxic TCA cycle-deficient tumors. Additionally, to study the putative alternative functions of FH, a recently identified alternative FH transcript (FHv) was characterized. FHv was found to contain instead of exon 1, an alternative exon 1b. Differential subcellular distribution, lack of FH enzyme activity, low mRNA expression compared to FH, and induction by cellular stress suggest FHv to have a role distinct from FH, for example in apoptosis or survival. However, the physiological significance of FHv requires further elucidation.

The role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia

Identification of genes predisposing to tumor syndromes has raised general awareness of tumorigenesis. Genetic testing of tumor susceptibility genes aids the recognition of individuals at increased risk of tumors. Identification of novel predisposing genes enables further studies concerning the classification of potential associated tumors and the definition of target patient group. Pituitary adenomas are common, benign neoplasms accounting for approximately 15% of all intracranial tumors. Accurate incidence estimation is challenging since a great portion of these adenomas are small and asymptomatic. Clinically relevant adenomas, that cause symptoms due to the expansion of the cell mass or the over-secretion of normally produced hormones, occur in approximately one of 1 000 individuals. Although the majority of pituitary adenomas are sporadic, a minority occur as components of familial syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1) and Carney complex (CNC). MEN1 syndrome is caused by germ-line mutations in the MEN1 gene, whereas most of the CNC patients carry the mutated protein kinase A (PKA) regulatory subunit-1-α (PRKAR1A) gene. Recently, other conditions predisposing to endocrine tumors have been identified: Pituitary Adenoma Predisposition (PAP) and MEN type 4 (MEN4). PAP was originally identified in a genetically homogeneous Finnish population. In a population based cohort from Northern Finland, aryl hydrocarbon receptor-interacting protein (AIP) gene mutations were found in 16% of all patients diagnosed with growth hormone (GH) producing pituitary adenoma, and in 40% of the subset of patients who were diagnosed under the age of 35 years. Since AIP mutations were originally described in a defined, homogeneous population from Northern Finland, it was relevant to study whether mutations also occur in more heterogeneous populations. In patient cohorts with different ethnic origins and variable clinical phenotypes, germ-line AIP mutations were detectable at low frequencies (range 0.8-7.4%). AIP mutation-positive patients were often diagnosed with a GH-producing adenoma at a young age, and usually had no family history of endocrine tumors. The low frequency of AIP mutations in randomly selected patients, and the lack of any family history of pituitary adenomas create a challenge for the identification of PAP patients. Our preliminary study suggests that AIP immunohistochemistry may serve as a pre-screening tool to distinguish between the AIP mutation-negative and the mutation-positive tumors. Tumors of various endocrine glands are components of MEN1 and CNC syndromes. Somatic MEN1 and PRKAR1A mutations in sporadic pituitary adenomas are rare, but occur in some of the other tumors related to these syndromes. The role of AIP mutations in endocrine neoplasia was studied and our results indicated that somatic AIP mutations are rare or non-existent in sporadic tumors of endocrine glands (0 of 111). Furthermore, germ-line AIP mutations in prolactin producing adenomas (2 of 9) confirmed the role of this pituitary tumor type in the PAP phenotype. Thyroid disorders are common in the general population, and the majority of them are sporadic. Interestingly, it has been suggested that thyroid disorders might be more common in PAP families. For this reason we studied germ-line AIP mutations in 93 index cases from familial non-medullary thyroid cancer (NMTC) families. The underlying gene or genes for familial NMTC have not been identified yet. None of the patients had any potentially pathogenic AIP mutation. This suggests that AIP is unlikely to play a role in familial NMTCs. A novel multiple endocrine syndrome was originally described in rats with phenotypic features of human MEN type 1 and 2. Germ-line mutations of cyclin-dependent kinase inhibitor 1B (CDKN1B also known as p27Kip1) gene were reported later in these rats and a germ-line mutation was also identified in one human family with MEN1-like phenotype (later named MEN4). To confirm the importance of this gene’s mutations in humans, we performed a mutation screening in MEN-like patients and in patients with pituitary adenoma. Our results indicate that CDKN1B/p27Kip1 mutations appear in a small portion of MEN1-like patients (one of 36), and that such mutations are rare or non-existent in both familial (0 of 19) and sporadic pituitary adenoma patients (0 of 50). In conclusion, this work strengthens the tumor susceptibility role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia. Clarifying the PAP phenotype facilitates the identification of potential AIP mutation carriers. Genetic counseling can be offered to the relatives and follow-up of the mutation carriers can be organized, hence an earlier diagnosis is feasible.

Hydrogen bonding with mono- and di-carbonyls

The electronic absorption and i.r. spectroscopic studies are reported for the hydrogen bonding systems involving alcohol and various ketones. It is shown that the hydrogen bonding abilities of ketones are determined by the extent of delocalization of the lone pair electrons in their non-bonding molecular orbitals. Evidence for the formation of very weak intermolecular hydrogen bonds between alcohol and the π-electron part of the dicarbonyls has also been presented from the i.r. studies in the 3400–3700 cm−1 region.

Portrait of Irene Kuhn Portraits; Women

Irene Kuhn and her family lived downstairs from the Roth family at Schneckenburgerstrasse 42, Munich. Her sister, and perhaps Irene also emigrated to London. Their mother Nelly Kuhn died in 1938. It is not known what happened to their father Albert.