Importance of animal models in schizophrenia research

Objective This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Method and Results Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Conclusions Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.

Genetic analysis of foot-and-mouth disease virus serotype A of Indian origin and detection of positive selection and recombination in leader protease- and capsid-coding regions

The leader protease (L-pro) and capsid-coding sequences (P1) constitute approximately 3 kb of the foot-and-mouth disease virus (FMDV). We studied the phylogenetic relationship of 46 FMDV serotype A isolates of Indian origin collected during the period 1968-2005 and also eight vaccine strains using the neighbour-joining tree and Bayesian tree methods. The viruses were categorized under three major groups - Asian, Euro-South American and European. The Indian isolates formed a distinct genetic group among the Asian isolates. The Indian isolates were further classified into different genetic subgroups (<5% divergence). Post-1995 isolates were divided into two subgroups while a few isolates which originated in the year 2005 from Andhra Pradesh formed a separate group. These isolates were closely related to the isolates of the 1970s. The FMDV isolates seem to undergo reverse mutation or onvergent evolution wherein sequences identical to the ancestors are present in the isolates in circulation. The eight vaccine strains included in the study were not related to each other and belonged to different genetic groups. Recombination was detected in the L-pro region in one isolate (A IND 20/82) and in the VP1 coding 1D region in another isolate (A RAJ 21/96). Positive selection was identified at aa positions 23 in the L-pro (P<0.05; 0.046*) and at aa 171 in the capsid protein VP1 (P<0.01; 0.003**).

The influence of animal mobility on the assumption of uniform distances in aerial line-transect surveys

Line-transect distance sampling is a widely used method for estimating animal density from aerial surveys. Analysis of line-transect distance data usually relies on a requirement that the statistical distribution of distances of animal groups from the transect line is uniform. We show that this requirement is satisfied by the survey design if all other assumptions of distance sampling hold, but it can be violated by consistent survey problems such as responsive movement of the animals towards or away from the observer. We hypothesise that problems with the uniform requirement are unlikely to be encountered for immobile taxa, but might become substantial for species of high mobility. We test evidence for non-uniformity using double-observer distance data from two aerial surveys of five species with a spectrum of mobility capabilities and tendencies. No clear evidence against uniformity was found for crabeater seals or emperor penguins on the pack-ice in East Antarctica, while minor non-uniformity consistent with responsive movement up to 30 m was found for Adelie penguins. Strong evidence of either non-uniformity or a failure of the capture-recapture validating method was found for eastern grey kangaroos and red kangaroos in Queensland.

Campylobacter Infections of Domestic Origin in Finland

Campylobacter jejuni and C. coli are the leading causes of human bacterial gastroenteritis in developed countries. Most human Campylobacter infections are sporadic and a seasonal peak in the distribution of infections can be seen in the summer months in several countries, including Finland. A variety of risk factors for Campylobacter infections have been identified; handling and eating poultry, drinking unpasteurized milk, contact with domestic animals, and travelling abroad. However, the relative importance of the different risk factors in sporadic cases of Campylobacter infection remains unknown. In most cases, the infection is self-limiting and no specific treatment is required. Campylobacter enteritis can cause a wide range of complications, including reactive arthritis (ReA) that is reported in 1-5% of the cases. Seven clinical microbiology laboratories serving different geographical areas of Finland, participated in this multi-centre study, conducted during a seasonal peak in 2002. In a matched case-control study, domestically-acquired sporadic Campylobacter infections from three geographical areas were collected. The final study comprised 100 cases and 137 controls. Risk factors for sporadic domestically-acquired Campylobacter infections were identified on the basis of a questionnaire; swimming in natural waters was found to be a novel risk factor for Campylobacter infection. Other independent risk factors were tasting or eating raw or undercooked meat and drinking untreated water from a dug well. The role of bacterial strain and host characteristics are not fully understood in Campylobacter infections. Exposure factors, demographical characteristics, and the serotype of the Campylobacter isolate may affect the severity of the enteritis. This cross-sectional study comprised 114 patients with C. jejuni enteritis, diagnosed in three clinical microbiology laboratories; most of the patients had participated in the previous case-control study. Swimming was associated with age ≤ 5 years and serotype Pen 6,7 was found significantly more often among patients reporting swimming. The geographical distribution among serotypes varied; serotype Pen 4-complex appeared more often in patients from urban areas and serotype Pen 21 among patients from more rural areas. Thus, risk factors and sources of infection for C. jejuni infection may vary among individuals depending on age and geographical location. The in vitro susceptibilities of C. jejuni and C. coli strains isolated from patients infected abroad (85 strains) or domestically (393 strains) revealed that susceptibility to erythromycin is still high, even among isolates of foreign origin. However, the novel antimicrobial agent telithromycin did not offer any advantage over erythromycin; isolates with high minimal inhibitory concentrations (MICs) for erythromycin also showed reduced susceptibility to telithromycin. Reduced susceptibility to fluoroquinolones was detected almost exclusively among isolates of foreign origin and half of these isolates with high MICs for fluoroquinolones also showed elevated MICs for doxycycline. Questionnaires concerning complications associated with C. jejuni enteritis were sent to patients two months after becoming ill; 201 patients from seven different geographical areas were included in the study. Musculoskeletal complications after C. jejuni infection were commonly reported by patients (39%). The incidence of classical ReA was 4% and that of Achilles enthesopathy and/or heel pain 9%. Other C. jejuni-associated reactive joint symptoms were commonly reported, however, due to their milder nature seldom seen and diagnosed by a physician. The severity of the enteritis may predict further complications; stomach ache during enteritis was connected to the development of later joint pain. Early antimicrobial treatment, within two days from the start of symptoms, shortened the duration of diarrhoea by two days but did not prevent later musculoskeletal complications. Campylobacter is an important human enteropathogen and causes a significant burden of illness. As the incidence of Campylobacter infections is high, the importance of the infection and the occurrence of complications will increase. This stresses the importance of understanding the risk factors for acquiring Campylobacter infection and how bacterial strain and host characteristics may affect the risk for infection. The role of antimicrobial treatment for acute Campylobacter enteritis seems to be marginal and should be used restrictively.

Evidence of bat origin for Menangle virus, a zoonotic paramyxovirus first isolated from diseased pigs

Menangle virus (MenPV) is a zoonotic paramyxovirus capable of causing disease in pigs and humans. It was first isolated in 1997 from stillborn piglets at a commercial piggery in New South Wales, Australia, where an outbreak of reproductive disease occurred. Neutralizing antibodies to MenPV were detected in various pteropid bat species in Australia and fruit bats were suspected to be the source of the virus responsible for the outbreak in pigs. However, previous attempts to isolate MenPV from various fruit bat species proved fruitless. Here, we report the isolation of MenPV from urine samples of the black flying fox, Pteropus alecto, using a combination of improved procedures and newly established bat cell lines. The nucleotide sequence of the bat isolate is 94% identical to the pig isolate. This finding provides strong evidence supporting the hypothesis that the MenPV outbreak in pigs originated from viruses in bats roosting near the piggery. © 2012 Printed in Great Britain.

Effects of seed origin latitude on the timing of height growth cessation and field performance of silver birch

The aim of this thesis was to increase our knowledge about the effects of seed origin on the timing of height growth cessation and field performance of silver birch from different latitudes, with special attention paid to the browsing damage by moose in young birch plantations. The effect of seed origin latitude and sowing time on timing of height growth cessation of first-year seedlings was studied in a greenhouse experiment with seven seed origins (lat. 58º - 67ºN). Variation in critical night length (CNL) for 50 % bud set within two latitudinally distant stands (60º and 67ºN) was studied in three phytotron experiments. Browsing by moose on 5-11 -year-old silver birch saplings from latitudinally different seed origins (53º - 67ºN) was studied in a field experiment in southern Finland. Yield and stem quality of 22-year-old silver birch trees of Baltic, Finnish and Russian origin (54º - 63ºN) and the effect of latitudinal seed transfers were studied in two provenance trials at Tuusula, southern and Viitasaari, central Finland. The timing of height growth cessation depended systematically on latitude of seed origin and sowing date. The more northern the seed origin, the earlier the growth cessation and the shorter the growth period. Later sowing dates delayed growth cessation but also shortened the growth period. The mean CNL of the southern ecotype was longer, 6.3 ± 0.2 h (95 % confidence interval), than that of the northern ecotype, 3.1 ± 0.3 h. Within-ecotype variance of the CNL was higher in the northern ecotype (0.484 h2) than in the southern ecotype (0.150 h2). Browsing by moose decreased with increasing latitude of seed origin and sapling height. Origins transferred from more southern latitudes were more heavily browsed than the more northern native ones. Southern Finnish seed origins produced the highest volume per unit area in central Finland (lat. 63º11'N). Estonian and north Latvian stand seed origins, and the southern Finnish plus tree origins, were the most productive ones in southern Finland (lat. 60º21'N). Latitudinal seed transfer distance had a significant effect on survival, stem volume/ha and proportion of trees with a stem defect. The relationship of both survival and stem volume/ha to the latitudinal seed transfer distance was curvilinear. Volume was increased by transferring seed from ca. 2 degrees of latitude from the south. A longer transfer from the south, and transfer from the north, decreased the yield. The proportion of trees with a stem defect increased linearly in relation to the latitudinal seed transfer distance from the south.

Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin

Missense and frameshift mutations in TRAF family member-associated NF-kappa-B activator (TANK)-binding kinase 1 (TBK1) have been reported in European sporadic and familial amyotrophic lateral sclerosis (ALS) cohorts. To assess the role of TBK1 in ALS patient cohorts of wider ancestry, we have analyzed whole-exome sequence data from an Australian cohort of familial ALS (FALS) patients and controls. We identified a novel TBK1 deletion (c.1197delC) in a FALS patient of Chinese origin. This frameshift mutation (p.L399fs) likely results in a truncated protein that lacks functional domains required for adapter protein binding, as well as protein activation and structural integrity. No novel or reported TBK1 mutations were identified in FALS patients of European ancestry. This is the first report of a TBK1 mutation in an ALS patient of Asian origin and indicates that sequence variations in TBK1 are a rare cause of FALS in Australia. © 2015 Elsevier Inc.

Cattle Teeth in Graves : Interpretations of animal bones found in Finnish inhumation graves (ca AD 550-1700)

The nature of a burial is always ritualistic. This is often forgotten when dealing with Finnish inhumation burials containing animal bones. Only the animal bones found close to the deceased have traditionally been thought to have a ritualistic purpose. The animal bones found in the filling of the grave, which is still part of the burial, has on the other hand, often been neglected in the previous research. In this Master s thesis I will discuss the function and interpretation of animal bones in graves. The base of this study is six sites, all of different nature, from Finland. Luistari in Eura is from the western coast and is dated to Late Iron Age (and possibly Medieval period), the Medieval hamlet of Finno is situated in Espoo which is situated on the southern coast. Two town burials, Turku and Porvoo, are also included in this study. The graves from Turku are dated to Late Medieval period and Early Renaissance, whereas the cemetery in Porvoo is from the 18th century. Visulahti in Mikkeli is from the Late Iron Age and represents Eastern Finnish burial tradition, the same as Suotniemi from Käkisalmi parish, which is nowadays part of Russia. While parts of the animal bones had already been analysed before, the author also analysed animal bones for the purpose of the present Master´s thesis. The bones were compared to the burial contexts, when possible. Based on the comparisons I have made interpretations which might explain the existence of animal bones in the graves. The interpretations are among others sacrifice, commemoration meals and animal burials. The site could also have been a settlement site prior to the graves, thus the bones in the graves would belong to the settlement phase. When comparing the date of the studied sites, the town burials are later and the animal bones are probably related to previous or contemporary use of the sites as graveyards. On top of this there does not seem to be much difference in burial tradition between Eastern and Western Finland, although at least from the hamlet burials of Finno there are aspects that could be linked to Eastern burials. In making the interpretations I have taken into consideration the aspects of belief during different time periods when they could be accounted as relevant. Also the problems with bone preservation were relevant and challenging for the study. Often only the hardest substance of the skeleton, namely teeth, has been preserved. For this reason the quality of the archaeological documentation was a key issue in this study. In producing quality interpretations of the animal bones in graves, the bones, contexts and their relationship to the surrounding site should be documented with care.

Synthetic studies in aromatic hemiterpenes of natural origin, Part 5: Synthesis of 6-acetyl-2,2-dimethyl-8-methoxychromene via benzylic oxidation route

The synthesis of 6-acetyl-2,2-dimethyl-8-methoxychromene (lc), a naturally occurring isomer of encecalin (la)h~s been described startilag from 2,2,6- trimethyl-8-methoxyclaromene (2e) which was obtained from creosol (4) in two steps involving condensation of the phenol with malic acid to the coumarin (3), followed by Grignard reaction with CHaMgI. The transformation of (2e) to the natural product (lc) was effeeted by oxidative dehydrogenation by DDQ of the 6-meth~r function to the formyl group (2f), Grignard reaction to the carbinol (2g) and finally its oxidation to the acetyl moiety (lc), the sequence of the essential steps schematically summarised as : Ar-CHs --* Ar-CHO --* Ar-CH (OH) CHs --* Ar---COCHs.

Investigation of the origin of glassiness in La0.5Sr0.5CoO3

A comprehensive magnetic study has been carried out on the two sets of La0.5Sr0.5CoO3 samples with a view to understand the origin of low temperature glassiness in the ferromagnetic state. The samples prepared by the conventional solid-state synthesis method show a low temperature shoulder in both dc magnetization as well as in the ac susceptibility measurements, which exhibit characteristics of glassiness such as the frequency dependence and memory effect. These observations suggest the existence of a distinct low temperature cluster-glass like phase within dominant ferromagnetic phase. But, once the same sample is properly homogenized by repeated grinding and annealing process, the low temperature glassy phase disappears, and it shows a pure ferromagnetic behavior. Our comparative study clearly reveals that the reentrant spin-glass like nature is not intrinsic to La0.5Sr0.5CoO3 system, in fact this is an outcome of the compositional inhomogeneity.

Solvation dynamics of tryptophan in water-dimethyl sulfoxide binary mixture: In search of molecular origin of composition dependent multiple anomalies

Experimental and simulation studies have uncovered at least two anomalous concentration regimes in water-dimethyl sulfoxide (DMSO) binary mixture whose precise origin has remained a subject of debate. In order to facilitate time domain experimental investigation of the dynamics of such binary mixtures, we explore strength or extent of influence of these anomalies in dipolar solvation dynamics by carrying out long molecular dynamics simulations over a wide range of DMSO concentration. The solvation time correlation function so calculated indeed displays strong composition dependent anomalies, reflected in pronounced non-exponential kinetics and non-monotonous composition dependence of the average solvation time constant. In particular, we find remarkable slow-down in the solvation dynamics around 10%-20% and 35%-50% mole percentage. We investigate microscopic origin of these two anomalies. The population distribution analyses of different structural morphology elucidate that these two slowing down are reflections of intriguing structural transformations in water-DMSO mixture. The structural transformations themselves can be explained in terms of a change in the relative coordination number of DMSO and water molecules, from 1DMSO:2H(2)O to 1H(2)O:1DMSO and 1H(2)O:2DMSO complex formation. Thus, while the emergence of first slow down (at 15% DMSO mole percentage) is due to the percolation among DMSO molecules supported by the water molecules (whose percolating network remains largely unaffected), the 2nd anomaly (centered on 40%-50%) is due to the formation of the network structure where the unit of 1DMSO:1H(2)O and 2DMSO:1H(2)O dominates to give rise to rich dynamical features. Through an analysis of partial solvation dynamics an interesting negative cross-correlation between water and DMSO is observed that makes an important contribution to relaxation at intermediate to longer times.

The Evolution of Animal Welfare and the 3Rs in Brazil, China, and India

Increasingly, scientific collaborations and contracts cross country borders. The need for assurance that the quality of animal welfare and the caliber of animal research conducted are equivalent among research partners around the globe is of concern to the scientific and laboratory animal medicine communities, the general public, and other key stakeholders. Therefore, global harmonization of animal care and use standards and practices, with the welfare of the animals as a cornerstone, is essential. In the evolving global landscape of enhanced attention to animal welfare, a widely accepted path to achieving this goal is the successful integration of the 3Rs in animal care and use programs. Currently, awareness of the 3Rs, their implementation, and the resulting animal care and use standards and practices vary across countries. This variability has direct effects on the animals used in research and potentially the data generated and may also have secondary effects on the country's ability to be viewed as a global research partner. Here we review the status of implementation of the 3Rs worldwide and focus on 3 countries-Brazil, China and India-with increasing economic influence and an increasing footprint in the biomedical research enterprise.