An Analysis of the Developmental Effects of the Embryonic Lethal Mutation X-23 in Drosophila

The developmental abnormalities resulting from a recessive, second chromosome, X-ray induced lethal mutation acting during the embryonic period of Drosophila melanogaster are described. Embryos of 18-22 hours of development were studied. The pattern of abnormalities indicates that the lethal effect was due to a general cessation of development during the period from 9-14 hours. There is a general failure of mid-gut and muscle development. The hypoderm, foregut and hindgut structures appear to have developed normally. In the absence of muscle development, hypodermal differentiation produces deep furrows which distort the structure of the embryo. Variation in the expression of the lethal genotype produces some differences in the morphogenetic movements of this period. Germ band shortening occurs regularly, dorsal closure is sometimes present and head involution is seen in one embryo. These differences are related to the degree of hypodermal differentiation and muscle development which occurs. This is interpreted to mean that the force generated by the thinning and spreading of the hypoderm is responsible for these movements. In the course of normal development this force is controlled by the concurrent differentiation of the musculature

An Analysis of Abnormal Development in the Cnbw-16 Stock of Drosophila melanogaster

Developmental abnormalities in the embryonic period resulting from cobalt-60 induced mutations in Drosophila melanogaster are discussed. Embryos of 16 hours of development were studied. Among 32 abnormal embryos found in 52 eggs in this stock (Cnbw-16), eight having a consistent pattern of abnormality were studied. These embryos, designated as Cnbw-16, type a, all show a failure of embryonic shortening and midgut development. Associated abnormalities permit interpretation concerning the nature of normal development in three areas: (1) nerve cord condensation, (2) embryonic shortening, and (3) muscle fiber differentiation. Nerve cord condensation is partial in the absence of embryonic shortening. This indicates that this process is the result of two activities: the mechanical process of embryonic shortening and the process of cell differentiation. Embryonic shortening fails in the presence of partial or complete somatic muscle development. This observation supports the idea that embryonic shortening is independent of the development of the somatic musculature. Muscle differentiation is arrested at several different points. Observations indicate that fusion of myoblasts occurs independently, but that fiber formation depends upon a normal contact with the apodemes

Unveiling the underlying drivers of Phanerozoic marine diversification

In investigating global patterns of biodiversity through deep time, many large-scale drivers of diversification have been proposed, both biotic and abiotic. However, few robust conclusions about these hypothesized effectors or their roles have been drawn. Here, we use a linear stochastic differential equation (SDE) framework to test for the presence of underlying drivers of diversification patterns before examining specific hypothesized drivers. Using a global dataset of observations of skeletonized marine fossils, we infer origination, extinction and sampling rates (collectively called fossil time series) throughout the Phanerozoic using a capture–mark–recapture approach. Using linear SDEs, we then compare models including and excluding hidden (i.e. unmeasured) drivers of these fossil time series. We find evidence of large-scale underlying drivers of marine Phanerozoic diversification rates and present quantitative characterizations of these. We then test whether changing global temperature, sea-level, marine sediment area or continental fragmentation could act as drivers of the fossil time series. We show that it is unlikely any of these four abiotic factors are the hidden drivers we identified, though there is evidence for correlative links between sediment area and origination/extinction rates. Our characterization of the hidden drivers of Phanerozoic diversification and sampling will aid in the search for their ultimate identities

Origin of the Term \u27Dude\u27

The book (261 pages, soft-covered) is intended as a scholarly study and therefore contains more detail than would appear in a book intended for a broad readership

On kaonic deuterium. Quantum field theoretic and relativistic covariant approach

We study kaonic deuterium, the bound K^-d state A_(K d). Within a quantum field theoretic and relativistic covariant approach we derive the energy level displacement of the ground state of kaonic deuterium in terms of the amplitude of K^-d scattering for arbitrary relative momenta. Near threshold our formula reduces to the well-known DGBT formula. The S-wave amplitude of K^-d scattering near threshold is defined by the resonances Lambda(1405), Sigma(1750) and a smooth elastic background, and the inelastic channels K^- d -> NY and K^- d -> NY pion, with Y = Sigma^(+/-), Sigma^0 and Lambda^0, where the final-state interactions play an important role. The Ericson-Weise formula for the S-wave scattering length of K^-d scattering is derived. The total width of the energy level of the ground state of kaonic deuterium is estimated using the theoretical predictions of the partial widths of the two-body decays A_(Kd) -> NY and experimental data on the rates of the NY-pair production in the reactions K^-d -> NY. We obtain Gamma_{1s} = (630 +/-100) eV. For the shift of the energy level of the ground state of kaonic deuterium we predict epsilon_(1s) = (353 +/-60)eV.Comment: 73 pages,10 figures, Latex, We have slightly corrected the contribution of the double scattering. The change of the S-wave scattering length of K^-d scattering does not go beyond the theoretical uncertainty, which is about 18

Isolation of Mycobacterium avium Subspecies paratuberculosis Reactive CD4 T Cells from Intestinal Biopsies of Crohn’s Disease Patients

Background: Crohn’s disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is unknown, but an excessive immune response to bacteria in genetically susceptible individuals is probably involved. The response is characterized by a strong Th1/Th17 response, but the relative importance of the various bacteria is not known. Methodology/Principal Findings: In an attempt to address this issue, we made T-cell lines from intestinal biopsies of patients with CD (n = 11), ulcerative colitis (UC) (n = 13) and controls (n = 10). The T-cell lines were tested for responses to various bacteria. A majority of the CD patients with active disease had a dominant response to Mycobacterium avium subspecies paratuberculosis (MAP). The T cells from CD patients also showed higher proliferation in response to MAP compared to UC patients (p,0.025). MAP reactive CD4 T-cell clones (n = 28) were isolated from four CD patients. The T-cell clones produced IL-17 and/or IFN-c, while minimal amounts of IL-4 were detected. To further characterize the specificity, the responses to antigen preparations from different mycobacterial species were tested. One T-cell clone responded only to MAP and the very closely related M. avium subspecies avium (MAA) while another responded to MAP, MAA and Mycobacterium intracellulare. A more broadly reactive T-cell clone reacted to MAP1508 which belongs to the esx protein family. Conclusions/Significance: The presence of MAP reactive T cells with a Th1 or Th1/Th17 phenotype may suggest a possible role of mycobacteria in the inflammation seen in CD. The isolation of intestinal T cells followed by characterization of their specificity is a valuable tool to study the relative importance of different bacteria in CD

Residual cognitive deficits 50 years after lead poisoning during childhood

The long term neurobehavioural consequences of childhood lead poisoning are not known. In this study adult subjects with a documented history of lead poisoning before age 4 and matched controls were examined with an abbreviated battery of neuropsychological tests including measures of attention, reasoning, memory, motor speed, and current mood. The subjects exposed to lead were inferior to controls on almost all of the cognitive tasks. This pattern of widespread deficits resembles that found in children evaluated at the time of acute exposure to lead rather than the more circumscribed pattern typically seen in adults exposed to lead. Despite having completed as many years of schooling as controls, the subjects exposed to lead were lower in lifetime occupational status. Within the exposed group, performance on the neuropsychological battery and occupational status were related, consistent with the presumed impact of limitations in neuropsychological functioning on everyday life. The results suggest that many subjects exposed to lead suffered acute encephalopathy in childhood which resolved into a chronic subclinical encephalopathy with associated cognitive dysfunction still evident in adulthood. These findings lend support to efforts to limit exposure to lead in childhood

A comparison of magnetic resonance imaging and neuropsychological examination in the diagnostic distinction of Alzheimer’s disease and behavioral variant frontotemporal dementia

The clinical distinction between Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) remains challenging and largely dependent on the experience of the clinician. This study investigates whether objective machine learning algorithms using supportive neuroimaging and neuropsychological clinical features can aid the distinction between both diseases. Retrospective neuroimaging and neuropsychological data of 166 participants (54 AD; 55 bvFTD; 57 healthy controls) was analyzed via a Naïve Bayes classification model. A subgroup of patients (n = 22) had pathologically-confirmed diagnoses. Results show that a combination of gray matter atrophy and neuropsychological features allowed a correct classification of 61.47% of cases at clinical presentation. More importantly, there was a clear dissociation between imaging and neuropsychological features, with the latter having the greater diagnostic accuracy (respectively 51.38 vs. 62.39%). These findings indicate that, at presentation, machine learning classification of bvFTD and AD is mostly based on cognitive and not imaging features. This clearly highlights the urgent need to develop better biomarkers for both diseases, but also emphasizes the value of machine learning in determining the predictive diagnostic features in neurodegeneration

Functional outcome is tied to dynamic brain states after mild to moderate traumatic brain injury

The current study set out to investigate the dynamic functional connectome in relation to long-term recovery after mild to moderate traumatic brain injury (TBI). Longitudinal resting-state functional MRI data were collected (at 1 and 3 months postinjury) from a prospectively enrolled cohort consisting of 68 patients with TBI (92% mild TBI) and 20 healthy subjects. Patients underwent a neuropsychological assessment at 3 months postinjury. Outcome was measured using the Glasgow Outcome Scale Extended (GOS-E) at 6 months postinjury. The 57 patients who completed the GOS-E were classified as recovered completely (GOS-E = 8; n = 37) or incompletely (GOS-E < 8; n = 20). Neuropsychological test scores were similar for all groups. Patients with incomplete recovery spent less time in a segregated brain state compared to recovered patients during the second visit. Also, these patients moved less frequently from one meta-state to another as compared to healthy controls and recovered patients. Furthermore, incomplete recovery was associated with disruptions in cyclic state transition patterns, called attractors, during both visits. This study demonstrates that poor long-term functional recovery is associated with alterations in dynamics between brain networks, which becomes more marked as a function of time. These results could be related to psychological processes rather than injury-effects, which is an interesting area for further work. Another natural progression of the current study is to examine whether these dynamic measures can be used to monitor treatment effects

Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study

Purpose - Whether an unfavorable lifestyle not only affects breast cancer risk, but also influences age at onset of breast cancer and survival, is under debate. Methods - In a population-based cohort, the Energy Balance and Breast Cancer Aspects throughout life (EBBA-Life) study, a total of 17,145 women were included. During follow-up, 574 women developed invasive breast cancer. Breast cancer cases were followed for an additional 9.1 years. Detailed medical records were obtained. Cox’s proportional hazard regression models were used to study the association between pre-diagnostic lifestyle factors (weight, physical activity, alcohol use, smoking, and hypertension), breast cancer risk, age at diagnosis, and survival. Results - At study entry, 34.3% of the participating women were overweight and 30.7% were physically inactive. Mean age at breast cancer diagnosis was 58.0 years, and 78.9% of the tumors were estrogen receptor positive. Among menopausal women who did not use hormone therapy and had an unfavorable lifestyle (3–5 unfavorable factors), compared with women who had a favorable lifestyle, we observed a twofold higher risk for postmenopausal breast cancer (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.23–3.69), and they were 3.4 years younger at diagnosis (64.8 versus 68.2 years, P = 0.032). Breast cancer patients with an unfavorable lifestyle, compared with patients with a favorable lifestyle, had almost a two times higher overall mortality risk (HR 1.96, 95% CI 1.01–3.80). Conclusions - Our study supports a healthy lifestyle improving breast cancer prevention, postponing onset of disease, and extending life expectancy among breast cancer patients