Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent ...evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.
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Oxidative Injury and Apoptosis of Dorsal Root Ganglion Neurons in Chronic Experimental Diabetic Neuropathy
Ann M. Schmeichel ,
James D. Schmelzer and
Phillip A. Low
From the Department of Neurology, ...Mayo Clinic, Rochester, Minnesota
Abstract
We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic
techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the
pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities
were present from the first month and persisted over 12 months. 8-Hydroxy-2′-deoxyguanosine labeling was significantly increased
at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three
time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant
increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings
support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target,
leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy.
Footnotes
Address correspondence and reprint requests to Phillip A. Low, Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester,
MN 55905. E-mail: low{at}mayo.edu .
Received for publication 25 March 2002 and accepted in revised form 23 September 2002.
8-OHdG, 8-hydroxy-2′-deoxyguanosine; DRG, dorsal root ganglion; EDN, experimental diabetic neuropathy; GSH, reduced glutathione;
STZ, streptozotocin; TUNEL, TdT-mediated dUTP-biotin nick end labeling.
DIABETES
Objective The purpose of this study is to document the incidence of vascular complications during anterior lumbar interbody fusion (ALIF) in 212 consecutive patients treated at the Scripps Clinic and ...determine what factors adversely affected outcome. Methods We reviewed the prospectively maintained database of all ALIF procedures performed at Scripps Clinic between August 2004 and June 2009. All procedures were performed by a spine surgeon in conjunction with a vascular surgeon who performed the exposure portion of the operation, and protected the vessels from injury during the instrumentation phase of the operation. Results Two hundred twelve ALIF operations were identified. The mean age of the patients was 53.8 years, and 120 (56.6%) were female. The mean body mass index (BMI) was 29.6 (range, 18.1 to 47.8). Twenty-two (10.4%) operations were performed at the L4-5 disc space, 149 (70.3%) at L5-S1, and 41 (19.3%) involved L4-L5 with L5-S1. The mean estimated blood loss (EBL) was 143 milliliters. There was a significant direct correlation between increasing BMI and EBL ( P = .018). Thirteen (6.1%) vascular injuries occurred of which five were major (38.5%). One major arterial injury (0.5%) occurred and required arterial thrombectomy and stent placement. Four of the major vascular injuries were venous in nature and required a multi-suture repair. The remaining eight injuries (61.5%) were venous, the majority of which required a suture repair. There were no mortalities. There was an increase risk of vascular injury when both L4-L5 and L5-S1 were exposed ( P = .003) and with the male gender ( P = .013). Calcification of the aorto-iliac system did not exert an effect on EBL or vascular injury. In four cases, the surgeon was unable to expose the appropriate disc levels. Conclusions Anterior exposure of the spine for ALIF can be performed safely with a team approach that includes a vascular surgeon. Preoperative evaluation by a vascular surgeon is advisable. Patients with increased BMI and bi-level exposures should be approached with caution.
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This volume presents 19 original essays addressing what is widely regarded as the most serious problem confronting America today and for years to come – terrorism – from the unique perspective of ...criminology. The chapters collected here address such issues as the prevention of terrorism, the applicability of community policing and routine activities models of crime to the problem of terrorism, how to balance liberty and security, and how to think about and manage the fear of terrorism, as well as the coordination of federal and local efforts to prevent and counter terrorism. Criminologists on Terrorism and Homeland Security will be of interest to anyone concerned about violence prevention in general and terrorism in particular, policing, prosecution, adjudication, sentencing and restorative justice.
The heterozygous mutation B6;C3-Opa1Q285STOP, which models autosomal dominant optic atrophy, leads to a 50% reduction in Opa1 transcript and protein in the mouse retina and neural tissues and is ...associated with visual dysfunction and structural changes in the murine retina and optic nerve. In this article we use this model to quantify and evaluate the dendritic morphology of retinal ganglion cells. Retinal ganglion cells in Opa1+/− mutant mice (n = 16) and accompanying age- and sex-matched controls (n = 11) (age ranges of <10, 10–15 and >20 months) were labelled DiOlistically with carbocyanine dyes to quantify changes in dendritic tree architecture as a function of age. We observed localized dendritic reduction to sublamina b of the inner plexiform layer without retinal ganglion cell loss, showing dendritic pruning of on- but not off-centre retinal ganglion cells, and this effect was exacerbated with age. The mean dendritic field area was reduced in on-centre retinal ganglion cells of 10- to 15-month-old mice (−24.24%; CV = 0.68; P < 0.05) and >20-month-old mice (−43.22%; CV = 0.75; P < 0.05) compared with age-matched wild-type controls. Similar changes were seen in average total dendritic length in on-centre retinal ganglion cells of 10- to 15-month-old mice (−31.66%; CV = 0.67; P < 0.05) and >20-month-old mice (−49.55%; CV = 0.63; P < 0.05). Sholl analysis showed a marked difference in the dendritic arborization of on-centre retinal ganglion cells in the 10- to 15-month-old group (area under the curve −21.67%; P > 0.05) and of the >20-month-old group (area under the curve −42.12%; P < 0.05) compared with the control group. There was no detectable change in dendritic morphology in <10-month-old Opa1+/− mutant mice compared with wild-type (P > 0.05). No significant changes (P > 0.05) were seen in off-centre retinal ganglion cells. Finally, there was also no significant change (P > 0.05) in the retinal ganglion cell count across all age groups. In conclusion, we show dendritic pruning in on-centre retinal ganglion cells of the Opa1+/− mouse model of autosomal dominant optic atrophy from as early as 10 months of age. These results highlight the importance of normal mitochondrial fusion balance, as influenced by the OPA1 protein in maintaining the dendritic morphology of retinal ganglion cells. Dendritic pruning precedes the onset of clinical visual loss and structural changes in the optic nerve in the absence of significant cell loss.
When performing a rapid manual interception, targets moving under constant motion are often intercepted with greater accuracy when compared to targets moving under accelerated motion. Usually, ...accelerated targets are timed too late and decelerating ones too early. The present experiment sought to investigate whether these differences in performance when intercepting targets moving under constant and accelerated motions change after a short period of practice. The task involved striking targets that moved along a straight track by moving forward a manipulandum that moved along a slide perpendicular to the target’s motion. Participants were allocated to one of the three experimental groups, defined according to the type of motion of the moving targets: constant speed, constant acceleration, and constant deceleration. Results showed that after some practice participants were able to intercept (positive and negative) accelerating moving targets as accurately as constant speed targets. These results suggest that people might be able to learn how to intercept accelerating targets, corroborating the results of some recent studies.
UV Chromosomes and Haploid Sexual Systems Coelho, Susana Margarida; Gueno, Josselin; Lipinska, Agnieszka Paulina ...
Trends in plant science,
09/2018, Volume:
23, Issue:
9
Journal Article
Peer reviewed
Open access
The evolution of sex determination continues to pose major questions in biology. Sex-determination mechanisms control reproductive cell differentiation and development of sexual characteristics in ...all organisms, from algae to animals and plants. While the underlying processes defining sex (meiosis and recombination) are conserved, sex-determination mechanisms are highly labile. In particular, a flow of new discoveries has highlighted several fascinating features of the previously understudied haploid UV sex determination and related mating systems found in diverse photosynthetic taxa including green algae, bryophytes, and brown algae. Analyses integrating information from these systems and contrasting them with classical XY and ZW systems are providing exciting insights into both the universality and the diversity of sex-determining chromosomes across eukaryotes.
Evolutionary theory predicts some common features shared by diploid XY or ZW chromosomes and UV chromosomes, but also some unique properties of UV systems.
Haploid U and V sex chromosomes are found in diverse eukaryotes and are likely to have originated from mating-type chromosomes.
The origin of sexes from mating types in volvocine algae can be traced between UV and mating-type chromosomes, and through conservation of the sex-determining gene MID.
New data from algae and early-diverging plants confirm evolutionary predictions and reveal unexpected properties of UV systems, such as asymmetric chromosome expansions and the accumulation of diploid-phase genes in pseudoautosomal regions.
MID-related or other classes of RWP-RK transcription factor genes in green algae and HMG domain-encoding genes in brown algae have emerged as candidate sex-determining genes.
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Background Cardiac rhythm abnormalities are a leading cause of morbidity and mortality in developed countries. Loss-of-function variants in the ANK2 gene can cause a variety of cardiac rhythm ...abnormalities including sinus node dysfunction, atrial fibrillation and ventricular arrhythmias (called the “ankyrin-B syndrome”). ANK2 encodes ankyrin-B, a molecule critical for the membrane targeting of key cardiac ion channels, transporters, and signalling proteins. Methods and Results Here, we describe a family with a reciprocal chromosomal translocation between chromosomes 4q25 and 9q26 that transects the ANK2 gene on chromosome 4 resulting in loss-of-function of ankyrin-B. Select family members with ankyrin-B haploinsufficiency due to the translocation displayed clinical features of ankyrin-B syndrome. Furthermore, evaluation of primary lymphoblasts from a carrier of the translocation showed altered levels of ankyrin-B as well as a reduced expression of downstream ankyrin-binding partners. Conclusions Thus, our data conclude that, similar to previously described ANK2 loss-of-function “point mutations”, large chromosomal translocations resulting in ANK2 haploinsufficiency are sufficient to cause the human cardiac ankyrin-B syndrome. The unexpected ascertainment of ANK2 dysfunction via the discovery of a chromosomal translocation in this family, the determination of the familial phenotype, as well as the complexities in formulating screening and treatment strategies are discussed.
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Building integration of photovoltaics (PV) has long been acknowledged as a key application for PV in developed countries. The avoided use of comparably priced alternatives such as polished or cut ...stone in commercial facades enables PV to be applied often at little or no additional cost. The use of semi-transparent PV modules within commercial atria represents an interesting application in this respect as they can be used to replace traditional shading solutions which often have a high maintenance burden. However, compared to standard double glazing, an element incorporating either mono or poly crystalline PV cells in a glass–glass construction comes at a cost premium. To justify such an application there must be significant added value in the PV solution. This paper critically appraises a semi-transparent PV atrium which links two administration buildings at the University of Southampton, enclosing the main campus reception desk. Choosing PV laminates for the atrium roof has multiple benefits for the building users and the wider University, such as electricity generation, solar shading, environmental and technology statements, enhanced comfort and prestigious office workspace. This paper compares alternative shading solutions for the atrium and discusses user perception of the building and the atrium’s impact on their personal workspace. It is shown that PV in commercial atria does not always have to be considered as a ‘luxury’ option. With appropriate consideration of added value factors its selection can be justified in terms of both cost and carbon footprint.
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