Evaluation of forensic genetics findings given activity level propositions: A review.

The evaluation of results of forensic genetic analyses given activity level propositions is an emerging discipline in forensic genetics. Although it is a topic with a long history, it has never been considered to be such a critically important topic for the field, as today. With the increasing sensitivity of analysis techniques, and advances in data interpretation using probabilistic models ('probabilistic genotyping'), there is an increasing demand on forensic biologists to share specialised knowledge to help recipients of expert information address mode and timing of transfer and persistence of traces in court. Scientists thereby have a critical role in the assessment of their findings in the context of the case. This helps the judiciary with activity level inferences in a balanced, robust and transparent way, when based on (1) proper case assessment and interpretation respecting the hierarchy of propositions (supported by, for example, the use of Bayesian networks as graphical models), (2) use of appropriate data to inform probabilities, and (3) reporting guidelines by international bodies. This critical review of current literature shows that with certain prerequisites for training and quality assurance, there is a solid foundation for evidence interpretation when propositions of interest are at the 'activity level'

The Stanley Foundation Bipolar Network: Results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres

The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in them SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar 11 disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration overtime. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapidcycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history. Copyright (c) 2003 S. Karger AG, Basel

Locally class-presentable and class-accessible categories

We generalize the concepts of locally presentable and accessible categories. Our framework includes such categories as small presheaves over large categories and ind-categories. This generalization is intended for applications in the abstract homotopy theory

Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson's disease and depression.

Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems

Partial reconstitution of cutaneous microvessels in long-term survivors after allogeneic bone marrow transplantation

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in acute and chronic disease. Immune-mediated vessel attack and subsequent microvessel loss have been observed in skin of patients with chronic GVHD. OBJECTIVES: To test whether long-term survivors (LTS) after allogeneic HSCT without cutaneous GVHD show signs of persistent vascular remodeling. METHODS: Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a median follow-up of 17 years (range 11-26). Five were currently classified as having chronic GVHD other than skin involvement. RESULTS: LTS showed no significant difference in median microvessel density and relative vessel size distribution pattern compared to healthy controls. Past experience of GVHD and current status of chronic GVHD other than skin involvement had no impact on vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic type and patients with lichen sclerosus have significant microvessel loss in the upper dermis. CONCLUSION: The complex therapy of allogeneic HSCT had no sustained effect on the microvascular architecture of LTS when clinicopathological evidence of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic GVHD recovers completely after resolution of chronic cutaneous GVHD

Developmental Changes in Pedunculopontine Nucleus (PPN) Neurons

The developmental decrease in rapid-eye-movement (REM) sleep in man occurs between birth and after puberty. We hypothesize that if this decrease in REM sleep does not occur, lifelong increases in REM sleep drive may ensue. Such disorders are characterized by hypervigilance and sensory-gating deficits, such as are present in postpubertal onset disorders like schizophrenia, panic attacks (a form of anxiety disorder), and depression. The decrease in REM sleep in the rat occurs between 10 and 30 days of age. We studied changes in size and physiological properties of pedunculopontine nucleus (PPN) cells involved in the control of arousal, i.e., waking and REM sleep. During the largest decrease in REM sleep (12–21 days), cholinergic PPN neurons doubled in cell area, the hypertrophy peaking at 15–16 days, then decreasing in area by 20–21 days. Noncholinergic PPN cells did not change in area during this period. We confirmed the presence of two populations of PPN neurons based on action potential (AP) duration, with the proportion of short-AP-duration cells increasing and long AP duration decreasing between 12 and 21 days. Most cholinergic and noncholinergic cells had short AP durations. Afterhyperpolarization (AHP) duration became segregated into long and short AHP duration after 15 days. Cells with short AP duration also had short AHP duration. The proportion of PPN cells with Ih current increased gradually, peaking at 15 days, then decreased by 21 days. These changes in morphological and physiological properties are discussed in relation to the developmental decrease in REM sleep

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

Plant volatiles play a major role in plant–insect interactions as defense compounds or attractants for insect herbivores. Recent studies have shown that endophytic fungi are also able to produce volatiles and this raises the question of whether these fungal volatiles influence plant–insect interactions. Here, we qualitatively investigated the volatiles released from 13 endophytic fungal species isolated from leaves of mature black poplar (Populus nigra) trees. The volatile blends of these endophytes grown on agar medium consist of typical fungal compounds, including aliphatic alcohols, ketones and esters, the aromatic alcohol 2-phenylethanol and various sesquiterpenes. Some of the compounds were previously reported as constituents of the poplar volatile blend. For one endophyte, a species of Cladosporium, we isolated and characterized two sesquiterpene synthases that can produce a number of mono- and sesquiterpenes like (E)-β-ocimene and (E)-β-caryophyllene, compounds that are dominant components of the herbivore-induced volatile bouquet of black poplar trees. As several of the fungus-derived volatiles like 2-phenylethanol, 3-methyl-1-butanol and the sesquiterpene (E)-β-caryophyllene, are known to play a role in direct and indirect plant defense, the emission of volatiles from endophytic microbial species should be considered in future studies investigating tree-insect interactions