Amyloid diseases at old age : a pathological, epidemiological, and genetic study

Along with the increased life span of individuals, the burden of old age-associated diseases has inevitably increased. Alzheimer s disease (AD), probably the most well known geriatric disease, belongs to the old age-associated amyloid diseases. The purpose of this study was to investigate the frequency, genetic and health-associated risk factors, mutual association, and amyloid proteins in two old age-associated amyloid disorders senile systemic amyloidosis (SSA) and cerebral amyloid angiopathy (CAA) as part of the prospective population-based Vantaa 85+ autopsy study on a Finnish population aged 85 years or more (Studies I-III), completed with a case report on a patient with advanced AGel amyloidosis (Study IV). The numbers of patients investigated in the studies (I-III) were 256, 74, and 63, respectively. The diagnosis and grading of amyloid were based upon histological examination of tissue samples obtained post mortem and stained with Congo red. The amyloid fibril and associated proteins were characterized by immunohistochemical staining methods. The genotype frequencies of 20 polymorphisms in 9 genes and information on health-associated risk factors in subjects with and without SSA and CAA were compared. In a Finnish population ≥ 95 years of age, SSA and CAA occurred in 36% and 49% of the subjects, respectively. In total, two-thirds of these very elderly individuals had SSA, CAA, or both. However, in only 14% of the population these two conditions co-occurred. In subjects 85 years or older, the prevalence of SSA was 25%. In this population, SSA was associated with age at the time of death (p=0.002), myocardial infarctions (MIs; p=0.004), the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (α2M) gene (p=0.042) and with the H2 haplotype of the tau gene (p=0.016). In contrast, the presence of CAA was strongly associated with APOE e4 (p=0.0003), with histopathological AD (p=0.0005), and with clinical dementia (p=0.01) in both e4+ (p=0.02) and e4- (p=0.06) individuals. Apart from demonstrating the amyloid fibril proteins, complement proteins 3d (C3d) and 9 (C9) were detected in the amyloid deposits of CAA and AGel amyloidosis, and α2M protein was found in fibrous scar tissue close to SSA. In conclusion, this first population based study on SSA shows that both SSA and CAA are common in very elderly individuals. Old age, MIs, the exon 24 polymorphism of the α2M gene, and H1/H2 polymorphism of the tau gene associate with SSA while clinical dementia and APOE ε4 genotype associate with CAA. The high prevalence of CAA, combined with its association with clinical dementia independent of APOE genotype, neuropathological AD, or SSA, also highlights its clinical significance in the very aged, among which the serious end stage complications of CAA, namely multiple infarctions and hemorrhages, are rare. The report on a patient having advanced AGel amyloidosis added knowledge on the disease and showed that this generally benign condition occasionally may lead to death. Further studies are warranted to confirm the findings in other populations. Also, the role of α2M and tau in the pathogenesis of SSA and the involvement of complement in the process of amyloid beta (Aβ) protein elimination from the brain remain to be clarified. Finally, the high prevalence of SSA in the elderly raises the need for prospective clinical studies to define its clinical significance.

Tombstone of Joseph Benjamin; Strangriede Cemetery, R83.8; Hannover Cemeteries Tombs

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Tombstones of Joseph Benjamin and Marianne Benjamin nee Sussmann; Strangriede Cemetery (R 83.8 and R 83.9); Hannover Cemeteries Tombs

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Tombstone of Joseph Benjamin; Strangriede Cemetery (R 83.8); Hannover Cemeteries Tombs

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Structure of (6S,13bR)-1,2,3,5,6,13b-hexahydro-6-isopropyl-8H-pyrrolo[1',2':1,2]pyrazino[3,4,-b]quinazoline-5,8-dione

C17H19N302, monoclinic, P21, a = 5.382 (1), b = 17.534(4), c = 8.198(1)/L ,8 = 100.46(1) °, Z= 2, d,, = 1.323, dc= 1.299 Mg m-3, F(000) = 316, /~(Cu .Ka) = 0.618 mm -1. R = 0.052 for 1284 significant reflections. The proline-containing cispeptide unit which forms part of a six-membered ring deviates from perfect planarity. The torsion angle about the peptide bond is 3.0 (5) ° and the peptide bond length is 1.313 (5)A. The conformation of the proline ring is Cs-Cf~-endo. The crystal structure is stabilized by C-H... O interactions.

The effect of temperature on height growth of Scots pine in northern Finland

The effect of temperature on height growth of Scots pine in the northern boreal zone in Lapland was studied in two different time scales. Intra-annual growth was monitored in four stands in up to four growing seasons using an approximately biweekly measurement interval. Inter-annual growth was studied using growth records representing seven stands and five geographical locations. All the stands were growing on a dry to semi-dry heath that is a typical site type for pine stands in Finland. The applied methodology is based on applied time-series analysis and multilevel modelling. Intra-annual elongation of the leader shoot correlated with temperature sum accumulation. Height growth ceased when, on average, 41% of the relative temperature sum of the site was achieved (observed minimum and maximum were 38% and 43%). The relative temperature sum was calculated by dividing the actual temperature sum by the long-term mean of the total annual temperature sum for the site. Our results suggest that annual height growth ceases when a location-specific temperature sum threshold is attained. The positive effect of the mean July temperature of the previous year on annual height increment proved to be very strong at high latitudes. The mean November temperature of the year before the previous had a statistically significantly effect on height increment in the three northernmost stands. The effect of mean monthly precipitation on annual height growth was statistically insignificant. There was a non-linear dependence between length and needle density of annual shoots. Exceptionally low height growth results in high needle-density, but the effect is weaker in years of average or good height growth. Radial growth and next year s height growth are both largely controlled by current July temperature. Nevertheless, their growth variation in terms of minimum and maximum is not necessarily strongly correlated. This is partly because height growth is more sensitive to changes in temperature. In addition, the actual effective temperature period is not exactly the same for these two growth components. Yet, there is a long-term balance that was also statistically distinguishable; radial growth correlated significantly with height growth with a lag of 2 years. Temperature periods shorter than a month are more effective variables than mean monthly values, but the improvement is on the scale of modest to good when applying Julian days or growing-degree-days as pointers.

Egg production in furnished cages

In the European Union, conventional cages for laying hens will be faded out at the beginning of 2012. The rationale behind this is a public concern over animal welfare in egg production. As alternatives to conventional cages, the European Union Council Directive 1999/74/EC allows non-cage systems and enriched (furnished) cages. Layer performance, behavior, and welfare in differently sized furnished cages have been investigated quite widely during recent decades, but nutrition of hens in this production system has received less attention. This thesis aims to compare production and feed intake of laying hens in furnished and conventional cages and to study the effects of different dietary treatments in these production systems, thus contributing to the general knowledge of furnished cages as an egg production system. A furnished cage model for 8 hens was compared with a 3-hen conventional cage. Three consecutive experiments each studied one aspect of layer diet: The first experiment investigated the effects of dietary protein/energy ratio, the second dietary energy levels, and the third the effects of extra limestone supplementation. In addition, a fourth experiment evaluated the effects of perches on feed consumption and behavior of hens in furnished cages. The dietary treatments in experiments 1 3 generally had similar effects in the two cage types. Thus, there was no evidence supporting a change in nutrient requirements for laying hens when conventional cages are replaced with small-group furnished cages. Moreover, the results from nutritional experiments conducted in conventional cages can be applied to small-group furnished cage systems. These results support the view that production performance comparable with conventional cages can be achieved in furnished cages. All of the advantages of cages for bird welfare are sustained in the small-group furnished cages used here. In addition, frequent use of perches and nests implies a wider behavioral repertoire in furnished cages than in conventional cages. The increase observed in bone ash content may improve bird welfare in furnished cages. The presence of perches diminished feed consumption during the prelaying period and enhanced the feed conversion ratio during the early laying period in furnished cages. However, as the presence or absence of perches in furnished cages had no significant effect on feed consumption after the prelaying period, the lower feed consumption observed in furnished cages than in conventional cages could be attributed to other factors, such as the presence of wood shavings or a nest box. The wider feed trough space per hen in conventional than in furnished cages may partly explain the higher feed consumption observed in conventional cages.

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

PURPOSE: In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS: A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS: Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. CONCLUSIONS: The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Structure of 2-(2,6-Dimethoxyphenyl)-2,5-dimethylbicyclo[3.2. l]octane-6,8-dione

C18H2204, orthorhombic, P212~21, a = 7.343 (4), b = 11.251 (4), c = 19.357 (4)A, Z = 4, Dr, ' = 1.20, D e = 1.254 g cm -3, F(000) = 648, p(Mo Ka) = 0.94 cm -~. X-ray intensity data were collected on a Nonius CAD-4 diffractometer and the structure was solved by direct methods. Full-matrix least-squares refinement gave R = 0.052 (R w = 0.045) for 1053 observed reflections. The stereochemical configuration at C(2) has been shown to be 2-exo-methyl-2-endo- (2,6-dimethoxyphenyl), i.e. (3) in contrast to the structure (2) assigned earlier based on its ~H NMR data.

Margarete Oppenheimer geb. Busch : 29. Mai 1883 - 8. August 1935.

Memorial book with the speeches by Leo Baeck and Hugo Jacobi.

Lost in Translation : Translation Mechanisms in Production of Cocksfoot Mottle Virus Proteins

The present study focuses on the translational strategies of Cocksfoot mottle virus (CfMV, genus Sobemovirus), which infects monocotyledonous plants. CfMV RNA lacks the 5'cap and the 3'poly(A) tail that ensure efficient translation of cellular messenger RNAs (mRNAs). Instead, CfMV RNA is covalently linked to a viral protein VPg (viral protein, genome-linked). This indicates that the viral untranslated regions (UTRs) must functionally compensate for the lack of the cap and poly(A) tail. We examined the efficacy of translation initiation in CfMV by comparing it to well-studied viral translational enhancers. Although insertion of the CfMV 5'UTR (CfMVe) into plant expression vectors improved gene expression in barley more than the other translational enhancers examined, studies at the RNA level showed that CfMVe alone or in combination with the CfMV 3'UTR did not provide the RNAs translational advantage. Mutation analysis revealed that translation initiation from CfMVe involved scanning. Interestingly, CfMVe also promoted translation initiation from an intercistronic position of dicistronic mRNAs in vitro. Furthermore, internal initiation occurred with similar efficacy in translation lysates that had reduced concentrations of eukaryotic initiation factor (eIF) 4E, suggesting that initiation was independent of the eIF4E. In contrast, reduced translation in the eIF4G-depleted lysates indicated that translation from internally positioned CfMVe was eIF4G-dependent. After successful translation initiation, leaky scanning brings the ribosomes to the second open reading frame (ORF). The CfMV polyprotein is produced from this and the following overlapping ORF via programmed -1 ribosomal frameshift (-1 PRF). Two signals in the mRNA at the beginning of the overlap program approximately every fifth ribosome to slip one nucleotide backwards and continue translation in the new -1 frame. This leads to the production of C-terminally extended polyprotein, which encodes the viral RNA-dependent RNA polymerase (RdRp). The -1 PRF event in CfMV was very efficient, even though it was programmed by a simple stem-loop structure instead of a pseudoknot, which is usually required for high -1 PRF frequencies. Interestingly, regions surrounding the -1 PRF signals improved the -1 PRF frequencies. Viral protein P27 inhibited the -1 PRF event in vivo, putatively by binding to the -1 PRF site. This suggested that P27 could regulate the occurrence of -1 PRF. Initiation of viral replication requires that viral proteins are released from the polyprotein. This is catalyzed by viral serine protease, which is also encoded from the polyprotein. N-terminal amino acid sequencing of CfMV VPg revealed that the junction of the protease and VPg was cleaved between glutamate (E) and asparagine (N) residues. This suggested that the processing sites used in CfMV differ from the glutamate and serine (S) or threonine (T) sites utilized in other sobemoviruses. However, further analysis revealed that the E/S and E/T sites may be used to cleave out some of the CfMV proteins.

Unusual products of oxidation with Cr(VI) of methyl 5-methyl-7-methoxy-8-isopropyl-3,4-2-naphthoate

Abstract is not available.

Analysis and computation of the oil film thickness between the piston ring and cylinder liner of an internal combustion engine

A study of the essential features of piston rings in the cylinder liner of an internal combustion engine reveals that the lubrication problem posed by it is basically that of a slider bearing. According to steady-flow-hydrodynamics, viz. Image the oil film thickness becomes zero at the dead centre positions as the velocity, U = 0. In practice, however, such a phenomenon cannot be supported by consideration of the wear rates of pistion rings and cylinder liners. This can be explained by including the “squeeze” action term in the

Sleep and self-regulation from birth to 7 years: A retrospective study of children with and without ADHD at 8-9 years

Objective To examine mean level differences, and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without ADHD at 8-9 years. Method This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort (n = 4109 analyzed). Children with and without ADHD were identified at age 8-9 years via parent-report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0-1, 2-3, 4-5 and 6-7 years of age. ANOVA was used to compare mean level differences in sleep problems, emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Results Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2-3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation two years later from 2-3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Conclusion Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.