Multifunctional Wing Motor Control of Song and Flight.

Multifunctional motor systems produce distinct output patterns that are dependent on behavioral context, posing a challenge to underlying neuronal control. Flies use their wings for flight and the production of a patterned acoustic signal, the male courtship song, employing in both cases a small set of wing muscles and corresponding motor neurons. We took first steps toward elucidating the neuronal control mechanisms of this multifunctional motor system by live imaging of muscle ensemble activity patterns during song and flight, and we established the functional role of a comprehensive set of wing muscle motor neurons by silencing experiments. Song and flight rely on distinct configurations of neuromuscular activity, with most, but not all, flight muscles and their corresponding motor neurons contributing to song and shaping its acoustic parameters. The two behaviors are exclusive, and the neuronal command for flight overrides the command for song. The neuromodulator octopamine is a candidate for selectively stabilizing flight, but not song motor patterns.

Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study.

Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age.

Engraftment of retroviral EGFP-transduced bone marrow in mice prevents rejection of EGFP-transgenic skin grafts.

We have investigated whether a state of tolerance toward EGFP-expressing skin tissue can be induced by prior establishment of EGFP molecular chimerism by transplant of gene-transduced bone marrow in mice. Irradiated (10 Gy) C57BL/6J mice were transplanted with bone marrow cells transduced with two different retroviral vectors encoding EGFP. EGFP-transduced, mock-transduced, and age-matched control mice received skin grafts from both C57BL/6 EGFP-transgenic (B6-EGFP. Tg) and MHC-mismatched B10.A donor mice at 8, 29, or 39 weeks after bone marrow transplantation. Although 14 of 17 control mice rejected EGFP.Tg skin grafts within 100 days, 24 of 25 mice receiving EGFP-expressing bone marrow cells accepted their B6-EGFP.Tg grafts out to 200 days after skin grafting, including animals with undetectable levels of EGFP expression in blood cells. The EGFP-transduced animals rejected third-party grafts from MHC-mismatched mice within 20 days, indicating that acceptance of the EGFP-expressing skin grafts was the result of the induction of specific and operational immune tolerance. Thus, our data indicate that (a) EGFP-expressing tissue elicits an immunological rejection in C57BL/6 mice and (b) tolerance can be induced by engrafting relatively small numbers of EGFP-transduced hematopoietic cells. These experiments utilizing EGFP as an immunogen point to the wider therapeutic potential of employing transplantation of gene-transduced hematopoietic cells for establishing immunological tolerance and thereby preventing rejection of gene-corrected cells and tissues.

Development and psychometric testing of the infant colic scale.

Novice researchers, when confronted with a clinical problem they want to study, are admonished by more experienced researchers to search the literature for an instrument that already has established reliability and validity, fits the problem of study, or that can be easily adapted. Sometimes, however, there is no such instrument available so the researcher has to develop a new instrument. The purpose of this article is to describe the steps required to develop and psychometrically test a new instrument. A new instrument, the Infant Colic Scale, is used as an example.