Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature ...with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle) expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas. For example, while the AONpP, APC and PPC all broadly expressed the deep cortical marker CTIP2, NOR1 (NR4a3) levels were higher in AONpP and DAARP-32 was more prevalent in the APC and PPC. Similar findings were encountered for superficial cortical markers: all three regions broadly expressed CUX1, but CART was only observed in the APC and PPC. Furthermore, regional variations were observed even within single structures (e.g., NOR1 was found primarily in in the dorsal region of AONpP and CART expression was observed in a discrete band in the middle of layer 2 of both the APC and PPC). Experiments using the mitotic marker EDU verified that the olfactory cortices and neocortex share similar patterns of neuronal production: olfactory cells that express markers found in the deep neocortex are produced earlier than those that express superficial makers. Projection neurons were filled by retrograde tracers injected into the olfactory bulb to see if olfactory neurons with deep and superficial markers had different axonal targets. Unlike the cerebral cortex, no specificity was observed: neurons with each of the transcription factors examined were found to be labelled. Together the results indicate that olfactory cortices are complex: they differ from each other and each is formed from a variable mosaic of neurons. The results suggest that the olfactory cortices are not merely a remnant architype of the primordial forebrain but varied and independent regions.
Suturing of the hernia aperture in laparoscopic ventral hernia repair has increased during the past decade. The primary aim of this is to restore the anatomy of the abdominal wall. Closure of the ...aperture, however, may cause additional tension in the abdominal wall which could increase postoperative pain. The aim of this study was to investigate whether suturing of the hernia aperture affects postoperative pain and hernia-site complications, including seroma, infection, pseudohernia, and mesh migration, 3 months after repair.
Some 192 patients with a midline hernia between 2 and 8 cm in transverse diameter were included in a randomized controlled double-blinded multicentre study. Patients were randomized to mesh repair with (intervention) or without (control) suturing of the hernia aperture before mesh placement. Patients completed the Ventral Hernia Pain Questionnaire before and 3 months after surgery. Abdominal wall pain and hernia-site complications were assessed 3 months after surgery.
Ninety-seven patients were randomized to the intervention group and 95 to the control group. Among all patients, median age and BMI was 56 years and 31 kg/m2 respectively. Overall pain experienced decreased by 3 months after operation (P < 0.001). There was no difference between groups regarding hernia-site complications or pain experienced during the past week (13 versus 23 patients; P = 0.111). Seroma and pseudohernia occurred in 13 and 11 patients in the intervention and control groups respectively (P = 0.975 and P = 0.977).
Restoration of the abdominal wall anatomy by suturing the hernia aperture before mesh placement does not increase the risk of hernia-site complication or pain 3 months after surgery. This implies that fascial suturing of the aperture can be justified if there are potential long-term benefits such as lower recurrence and/or complication rates. Registration number: ISRCTN51495042 (http://www.controlled-trials.com).
The first double diffractive cross-section measurement in the very forward region has been carried out by the TOTEM experiment at the LHC with a center-of-mass energy of sqrts=7 TeV. By utilizing ...the very forward TOTEM tracking detectors T1 and T2, which extend up to |η|=6.5, a clean sample of double diffractive pp events was extracted. From these events, we determined the cross section σDD=(116±25) μb for events where both diffractive systems have 4.7<|η|min<6.5.
COG0523 proteins, also known as nucleotide-dependent metallochaperones, are a poorly understood class of small P-loop G3E GTPases. Multiple family members play critical roles in bacterial pathogen ...survival during an infection as part of the adaptive response to host-mediated “nutritional immunity.” Our understanding of the structure, dynamics, and molecular-level function of COG0523 proteins, apart from the eukaryotic homolog, Zng1, remains in its infancy. Here, we use X-ray absorption spectroscopy to establish that Acinetobacter baumannii (Ab) ZigA coordinates ZnII using all three cysteines derived from the invariant CXCC motif to form an S3(N/O) coordination complex, a feature inconsistent with the ZnII-bound crystal structure of a distantly related COG0523 protein of unknown function from Escherichia coli, EcYjiA. The binding of ZnII and guanine nucleotides is thermodynamically linked in AbZigA, and this linkage is more favorable for the substrate GTP relative to the product GDP. Part of this coupling originates with nucleotide-induced stabilization of the G-domain tertiary structure as revealed by global thermodynamics measurements and hydrogen-deuterium exchange mass spectrometry (HDX-MS). HDX-MS also reveals that the HDX behavior of the G2 (switch 1) loop is highly sensitive to nucleotide status and becomes more exchange labile in the GDP (product)-bound state. Significant long-range perturbation of local stability in both the G-domain and the C-terminal domain define a candidate binding pocket for a client protein that appears sensitive to nucleotide status (GDP versus GTP). We place these new insights into the structure, dynamics, and energetics of intermolecular metal transfer into the context of a model for AbZigA metallochaperone function.
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The Pig Olfactory Brain: A Primer Brunjes, Peter C; Feldman, Sanford; Osterberg, Stephen K
Chemical senses,
06/2016, Letnik:
41, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview ...of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals.
Background
Intermittent claudication is associated with significant impairment of health‐related quality of life. The use of revascularization techniques to improve health‐related quality of life ...remains controversial.
Methods
Patients with intermittent claudication due to iliac or femoropopliteal peripheral artery disease were enrolled in the IRONIC trial. They were randomized to either best medical therapy (BMT), including a structured, non‐supervised exercise programme, or revascularization with either endovascular or open techniques in addition to BMT. The primary outcome was health‐related quality of life at 2 years assessed using the Short Form 36 (SF‐36®) questionnaire. Secondary outcomes included VascuQoL questionnaire results, treadmill walking distances and achievement of patient‐specified treatment goals.
Results
Both randomized groups had improved health‐related quality of life and treadmill walking distance at 2‐year follow‐up. Overall SF‐36® physical component summary score, three SF‐36® physical domain scores, overall VascuQoL score, and three of five VascuQoL domain scores showed significantly greater improvement in the group that also received invasive treatment. Intermittent claudication distance on a graded treadmill improved more in the revascularization + BMT group (117 versus 55 m; P = 0·003) whereas maximum walking distance and 6‐min walk test distance were similar. Some 44 per cent of patients in the revascularization + BMT group reported they had fully achieved their treatment goal versus 10 per cent in the BMT group.
Conclusion
A revascularization strategy with unsupervised exercise improved health‐related quality of life and intermittent claudication distance more than standard BMT and an unsupervised exercise programme in patients with lifestyle‐limiting claudication. Registration number: NCT01219842 (http://www.clinicaltrials.gov).
Revascularization better than unsupervised exercise alone
Current Swedish guidelines recommend that carotid endarterectomy should be performed within 14 days of a qualifying neurological event, but it is not clear if very urgent surgery after an event is ...associated with increased perioperative risk. The aim of this study was to determine how the time between the event and carotid endarterectomy affects the procedural risk of mortality and stroke.
We prospectively analyzed data on all patients who underwent carotid endarterectomies for symptomatic carotid stenosis between May 12, 2008, and May 31, 2011, with records in the Swedish Vascular Registry (Swedvasc). Patients were divided according to time between the qualifying event and surgery (0-2 days, 3-7 days, 8-14 days, 15-180 days). Stroke rate and mortality at 30 days postsurgery were determined.
We analyzed data for 2596 patients and found that the combined mortality and stroke rate for patients treated 0 to 2 days after qualifying event was 11.5% (17 of 148) versus 3.6% (29 of 804), 4.0% (27 of 677), and 5.4% (52 of 967) for the groups treated at 3 to 7 days, 8 to 14 days, and 15 to 180 days, respectively. In a multivariate analysis, time was an independent risk factor for perioperative complications: patients treated at 0 to 2 days had a relative OR of 4.24 (CI, 2.07-8.70; P<0.001) compared with the reference 3- to 7-day group.
In this study of patients treated for symptomatic carotid disease, it was safe to perform surgery as early as Day 3 after a qualifying neurological event in contrast to patients treated within 0 to 2 days, which has a significantly increased perioperative risk.
Single crystal CVD (scCVD) diamond is an attractive material for particle detection in high energy physics for its good time resolution and reported outstanding radiation tolerance. In addition to ...direct signal loss via charge carrier trapping, polarization effect, caused by non-homogeneous filling of trap defects, is a known cause of signal degradation in irradiated scCVD diamond. This phenomenon was studied by intentionally polarizing irradiated diamonds. Even the relatively lightly irradiated (1014 protons/cm2) diamonds exhibited strong enough polarization to collapse the electric field with moderate rate of 5 MeV alpha particles. The transient current measurements were reproduced with TCAD simulations. The hypothesis that the polarization is caused by single neutral defect type in the bulk, was tested using two generic models. Neither one has a satisfactory agreement with the measurement data, which indicates that trapping at the interfaces play a significant role in space charge polarization.
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•Space charge polarization was studied with irradiated single crystal diamond sensors.•Full collapse of the electric field was observed for all irradiated samples.•To remove polarization in low fluence samples switching bias voltage on-off effective•Polarization very likely cannot be explained by trapping in the bulk only.
Accumulation of intimal smooth muscle cells (SMC) is an important event in vein graft-stenosis. Different SMC sources have been reported, but their interrelations have been poorly studied. In a mouse ...vein graft model we investigated whether recipient-derived intimal SMCs are recruited from the surrounding tissue and whether blockage of SMC recruitment from the surrounding tissue and/or the donor vein will reduce neointimal formation.
To detect recipient-derived cells, wild-type veins were implanted into ROSA26 transgenic mice. To block cell recruitment from the surrounding tissue, implanted veins were isolated with a tube-shaped plastic film. To exclude vein-derived cells in the neointimal formation, acellular veins were implanted.
In vein grafts isolated from the surrounding tissue the recipient contribution became minimal, but the total number of SMCs was not decreased. Acellular grafts contained an equal number of intimal SMCs as cellular controls after 4 weeks. Isolation of acellular grafts from the surrounding tissue decreased the number of intimal SMCs by 90%.
Recipient-derived SMCs are mainly recruited from the surrounding tissue. Cell recruitment from either the vein or the surrounding tissue is enough to form a neointima. Therefore, a simultaneous inhibition of both these sources is needed to reduce accumulation of intimal SMCs.
Objectives The risk of recurrent stroke in patients with symptomatic carotid artery stenosis is highest in the first weeks after a transient ischemic attack (TIA) or minor stroke and can be reduced ...with carotid endarterectomy (CEA). The optimal timing of CEA remains a controversial issue since very urgent CEA is associated with an increased procedural risk. The aim of this study was to determine the risk of very early recurrent stroke in a population with symptomatic high grade carotid stenosis. Methods Data were analyzed on all patients with ocular TIA, TIA, or minor stroke with >70% carotid stenosis as assessed by carotid ultrasound at Sahlgrenska University Hospital during the periods 2004–2006 and 2010–2012. The two time periods were chosen to minimize selection bias and to analyze changes over time. The risk of recurrent stroke within 30 days of the referring event was assessed. Results 397 patients with symptomatic carotid stenosis were identified. The risk of recurrent stroke in the total cohort was 2.0% (CI 95% 0.6–3.4) by day 2, 4.0% (CI 95% 2.0–5.9) by day 7, and 7.5% (CI 95% 4.4–10.6) by day 30. There was no significant difference between the two time periods. Patients with minor stroke had a significantly higher risk of recurrent stroke than patients with TIA or ocular TIA as the referring event. Conclusions The data suggest that the early risk of recurrent stroke in symptomatic significant carotid stenosis is not as high as some earlier studies have shown. The risk is similar to several studies in which a modern medical treatment regime could be assumed.
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