Search

The Andean blackberry (Rubus glaucus Benth.) is a promissory fruit crop for Colombia with potential to become an international commodity due to its high nutritional and nutraceutical value. Farmer genotypes from the national R. glaucus collection were selected from eight outstanding accessions according to their nutritional and agronomic value, for distribution among local producers. The goal of this work is to evaluate the genomic fingerprint by AFLP analysis of these elite genotypes using three primer combinations. From 179 total amplified loci produced by the three combinations, 20% resulted polymorphic. The EAGG/MCTT combination was the most informative with a 32% polymorphism and greater discrimination power. The genotypes tested showed a high average similarity (96%) and the accessions San Antonio and ILS-1863 formed independent groups with good statistical support in the clustering analysis. The remaining accessions did not form discrete groups with good support (

Abstract Background Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression. Methods PBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106 DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC. Results Immature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migrate in vitro toward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p < 0.05). The presence of CD8+T lymphocytes specific to gp100 and Melan A/MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by stimulated PBMC, and faster melanoma progression after lymph nodes surgery (p = 0.04). With a mean follow-up of 49.5 months post-surgery, one stage IIC patient and 7/8 stage III patients remain NED but 7/7 stage IV patients have progressed. Conclusion We conclude that DC/Apo-Nec vaccine is safe, well tolerated and it may induce specific immunity against melanoma Ags. Patients with a low-producing IL-10 polymorphism appear to have a worst prognosis. Trial registration Clinicaltrials.gov (NHI) NCT00515983

Abstract Background To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH). Methods Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. Results We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase. Conclusion Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.

Context: Neighborhood and built environment encompass one key area of the Social Determinants of Health (SDOH) and is frequently assessed using area-level indices., Objective: We sought to systematically review the pediatric surgery literature for use of commonly applied area-level indices and to compare their utility for prediction of outcomes., Data Sources: A literature search was conducted using PubMed, Ovid MEDLINE, Ovid MEDLINE Epub Ahead of Print, PsycInfo, and an artificial intelligence search tool (1/2013-2/2023)., Study Selection: Inclusion required pediatric surgical patients in the US, surgical intervention performed, and use of an area-level metric., Data Extraction: Extraction domains included study, patient, and procedure characteristics., Results: Area Deprivation Index is the most consistent and commonly accepted index. It is also the most granular, as it uses Census Block Groups. Child Opportunity Index is less granular (Census Tract), but incorporates pediatric-specific predictors of risk. Results with Social Vulnerability Index, Neighborhood Deprivation Index, and Neighborhood Socioeconomic Status were less consistent., Limitations: All studies were retrospective and quality varied from good to fair., Conclusions: While each index has strengths and limitations, standardization on ideal metric(s) for the pediatric surgical population will help build the inferential power needed to move from understanding the role of SDOH to building meaningful interventions towards equity in care., Type of Study: Systematic Review., Level of Evidence: Level III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Corals establish symbiotic relationships with microorganisms, especially endosymbiotic photosynthetic algae. Although other microbes have been commonly detected in coral tissues, their identity and beneficial functions for their host are unclear. Here, we confirm the beneficial outcomes of the inoculation of bacteria selected as probiotics and use fluorescence in situ hybridization (FISH) to define their localization in the coral Pocillopora damicornis . Our results show the first evidence of the inherent presence of Halomonas sp. and Cobetia sp. in native coral tissues, even before their inoculation. Furthermore, the relative enrichment of these coral tissue-associated bacteria through their inoculation in corals correlates with health improvements, such as increases in photosynthetic potential, and productivity. Our study suggests the symbiotic status of Halomonas sp. and Cobetia sp. in corals by indicating their localization within coral gastrodermis and epidermis and correlating their increased relative abundance through active inoculation with beneficial outcomes for the holobiont. This knowledge is crucial to facilitate the screening and application of probiotics that may not be transient members of the coral microbiome., Importance: Despite the promising results indicating the beneficial outcomes associated with the application of probiotics in corals and some scarce knowledge regarding the identity of bacterial cells found within the coral tissue, the correlation between these two aspects is still missing. This gap limits our understanding of the actual diversity of coral-associated bacteria and whether these symbionts are beneficial. Some researchers, for example, have been suggesting that probiotic screening should only focus on the very few known tissue-associated bacteria, such as Endozoicomonas sp., assuming that the currently tested probiotics are not tissue-associated. Here, we provide specific FISH probes for Halomonas sp. and Cobetia sp., expand our knowledge of the identity of coral-associated bacteria and confirm the probiotic status of the tested probiotics. The presence of these beneficial microorganisms for corals (BMCs) inside host tissues and gastric cavities also supports the notion that direct interactions with the host may underpin their probiotic role. This is a new breakthrough; these results argue against the possibility that the positive effects of BMCs are due to factors that are not related to a direct symbiotic interaction, for example, that the host simply feeds on inoculated bacteria or that the bacteria change the water quality., Competing Interests: The authors declare no conflict of interest.

Background: Short bowel syndrome is the most common cause of intestinal failure, with morbidity and mortality linked to remanent small intestine length. There is no current standard for noninvasive bowel length measurement., Materials and Methods: The literature was systematically searched for articles describing measurements of small intestine length from radiographic studies. Inclusion required reporting intestinal length as an outcome and use of diagnostic imaging for length assessment compared to a ground truth. Two reviewers independently screened studies for inclusion, extracted data, and assessed study quality., Results: Eleven studies met the inclusion criteria and reported small intestinal length measurement using four imaging modalities: barium follow-through, ultrasound, computed tomography, and magnetic resonance. Five barium follow-through studies reported variable correlations with intraoperative measurements (r = 0.43-0.93); most (3/5) reported underestimation of length. US studies (n = 2) did not correlate with ground truths. Two computed tomography studies reported moderate-to-strong correlations with pathologic (r = 0.76) and intraoperative measurements (r = 0.99). Five studies of magnetic resonance showed moderate-to-strong correlations with intraoperative or postmortem measurements (r = 0.70-0.90). Vascular imaging software was used in two studies, and a segmentation algorithm was used for measurements in one., Conclusions: Noninvasive measurement of small intestine length is challenging. Three-dimensional imaging modalities reduce the risk of length underestimation, which is common with two-dimensional techniques. However, they also require longer times to perform length measurements. Automated segmentation has been trialed for magnetic resonance enterography, but this method does not translate directly to standard diagnostic imaging. While three-dimensional images are most accurate for length measurement, they are limited in their ability to measure intestinal dysmotility, which is an important functional measure in patients with intestinal failure. Future work should validate automated segmentation and measurement software using standard diagnostic imaging protocols., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The ever-increasing number and variation of raw materials utilized to provide alternative feed formulations continues to allow for a more sustainable and flexible approach. Testing all these options in vivo is still the most robust and reliable manner to pick the best raw material candidates, but it requires the use of large numbers of animals and is time-consuming and expensive. Therefore, we are developing an in vitro platform that can provide a reliable evaluation of new ingredients. The main aim of this work was to combine an in vitro digestion protocol of extruded, commercially relevant aquafeeds with the exposure of intestinal epithelial cells to the extracted bio-available fraction (BAF). The results show that 250,000 cells/cm 2 represents the optimal seeding density and that up to 50% BAF concentration for up to 24 h had no negative effects on the epithelial barrier morphology and function. It is possible to determine amino acid digestibility and bioavailability in all the experimental conditions (with and without BSA, at 25% and 50% dilution) and at all time points (0, 6, and 24 h). However, BAF concentration, the medium used for its dilution, and the length of exposure to the different epithelial cell lines can all influence the results and, therefore, must be selected according to the final aim of the experiment.

Pyroelectric infrared sensors (PIR) are widely used as infrared (IR) detectors due to their basic implementation, low cost, low power, and performance. Combined with a Fresnel lens, they can be used as a binary detector in applications of presence and motion control. Furthermore, due to their features, they can be used in autonomous intelligent devices or included in robotics applications or sensor networks. In this work, two neural processing architectures are presented: (1) an analog processing approach to achieve the behavior of a presynaptic neuron from a PIR sensor. An analog circuit similar to the leaky integrate and fire model is implemented to be able to generate spiking rates proportional to the IR stimuli received at a PIR sensor. (2) An embedded postsynaptic neuron where a spiking neural network matrix together with an algorithm based on digital processing techniques is introduced. This structure allows connecting a set of sensors to the post-synaptic circuit emulating an optic nerve. As a case study, the entire neural processing approach presented in this paper is applied to optical flow detection considering a four-PIR array as input. The results validate both the spiking approach for an analog sensor presented and the ability to retrieve the analog information sent as spike trains in a simulated optic nerve.

Introduction: Two-stage free functional muscle transfers for long-standing facial palsy can yield unpredictable results. Earlier studies have demonstrated incomplete regeneration across neurorrhaphies in native nerve and higher donor axonal counts correlating with improved outcomes but axonal count in nerve grafts have not been as thoroughly reviewed. To investigate the impact of varying axonal counts in autologous grafts on functional outcomes of repair., Materials and Methods: Animals were allocated into three groups: Direct Nerve Repair (DNR, n = 50), Small Nerve Graft (SNG, n = 50), and Large Nerve Graft (LNG, n = 50). All grafts were inset into the Posterior Auricular Nerve with ear movement recovery (EMR) monitored as functional outcome. At various postoperative weeks (POWs), excised specimens were imaged with electron microscopy. Axonal counts were measured proximal to, distal (DAC) to, and within grafts. Total Success Ratio (TSR) was calculated., Results: In DNR, DAC was significantly lower than proximal axonal counts at all POWs, with maximum TSR of 80%. TSR for LNG and SNG were significantly lower at all POWs when compared to DNR, with maximums of 56% and 38%, respectively. LNG had a significantly larger DAC than SNG at POW12 and beyond. A direct relationship was present between DAC and EMR for all values., Conclusions: Higher native axonal count of autologous nerve grafts resulted in higher percentage of regeneration across neurorrhaphies., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

There exists a dichotomy in regenerative capacity between the PNS and CNS, which poses the question - where do cranial nerves fall? Through the discussion of the various cells and processes involved in axonal regeneration, we will evaluate whether the assumption that cranial nerve regeneration is analogous to peripheral nerve regeneration is valid. It is evident from this review that much remains to be clarified regarding both PNS and CNS regeneration. Furthermore, it is not clear if cranial nerves follow the PNS model, CNS model or possess an alternative novel regenerative process altogether. Future research should continue to focus on elucidating how cranial nerves regenerate; and the various cellular interactions, molecules and pathways involved.

Split-thickness skin-grafts are a mainstay of burn management. Studies suggest no benefit to using thick (0.025 inch) over standard (0.012-0.020 inch) grafts, and some support the use of thin (0.008 inch) over standard thickness. Data on the use of even thinner grafts is scarce. This study reviewed outcomes of burn patients treated with thin (0.008-0.011 inch) and ultra-thin (≤0.007 inch) grafts. Retrospective review of records from July 2012 to June 2016 included patients who sustained operative burns treated by a single surgeon. Patients were excluded for nonoperative injuries, inhalational injuries, or prolonged hospitalizations. Outcome measures were compared between thin and ultra-thin groups. One-hundred twenty-eight patients met inclusion criteria; 35 received thin split-thickness skin-grafts while 93 received ultra-thin. Cohort analysis demonstrated equivalent graft-take, time to reepithelialization, and functional outcomes. Time to donor-site healing was significantly faster in the ultra-thin cohort (P = .04). Of those with functional outcomes recorded, 88.1% had good-excellent function and 11.9% retained a limitation in function as designated in physical therapy notes. There were fewer complications overall (P = .004) and a lower incidence of hypertrophic scarring (P = .025) in the ultra-thin cohort. This study presents a single-surgeon experience with thin and ultra-thin split-thickness skin-grafts. These grafts are exhibit excellent graft-take and few complications. There was no correlation between thickness and functional outcome at the time of physical therapy discharge. Donor-site reepithelialization was faster with ultra-thin grafts, which may be important in patients with large burns and limited donor sites., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Current microsurgical training courses average 5 consecutive 8-hour days and cost US $1500 to US $2500/individual, making training a challenge for residents who are unable to take leave from clinical duties. This residency-integrated microsurgery course was designed for integration with a residency program, averaging 3 hours/week over 7 weeks. This allows for one-on-one training, beginning with synthetic tissue and concluding with in vivo stimulation. This study was performed to validate this longitudinal training course., Methods: After recruitment and before the start of coursework, subjects completed a baseline anastomosis without guidance and a survey regarding microsurgical experience. Subjects completed approximately 3 hours/week of practical exercises. Weeks 1 to 5 used synthetic models, whereas 6 to 7 used in vivo rodent models. Nine minimum anastomoses of increasing complexity were completed and assessed with the Anastomosis Lapse Index and the Stanford Microsurgery and Residency Training scale. Scoring was performed by 3 independent reviewers and averaged for comparison., Results: Five subjects completed the course for study. Presurvey results showed an average confidence in theoretical knowledge of 2/5; technical ability to perform procedures, 1.8/5; and ability to manage complications, 1.8/5. Postsurvey revealed confidence in theoretical knowledge of 2.5/5; technical ability to perform procedures, 2.25/5; and ability to manage complications, 2.25/5. None of these differences were significant. Each individual component of the Stanford Microsurgery and Residency Training scale scoring system improved postcourse with P < 0.05, and overall performance score improved from an average of 2.6 to 3.9 (P = 0.006). The total number of errors recorded using the Anastomosis Lapse Index reduced from 6.58 to 3.41 (P = 0.02). Time to completion reduced from an average of 28 minutes, 8 seconds to 24 minutes, 5 seconds (P = 0.003)., Conclusions: Despite a lack in significant confidence improvement, completion of the residency-integrated microsurgery course leads to significant and quantifiable improvement in resident microsurgical skill and efficiency.

Variant Creutzfeldt-Jakob disease (vCJD) is caused by prion infection with bovine spongiform encephalopathy and can be transmitted by blood transfusion. Protein misfolding cyclic amplification (PMCA) can detect prions in blood from vCJD patients with 100% sensitivity and specificity. To determine whether PMCA enables prion detection in blood during the preclinical stage of infection, we performed a blind study using blood samples longitudinally collected from 28 control macaques and 3 macaques peripherally infected with vCJD. Our results demonstrate that PMCA consistently detected prions in blood during the entire preclinical stage in all infected macaques, without false positives from noninfected animals, when using the optimized conditions for amplification of macaque prions. Strikingly, prions were detected as early as 2 months postinoculation (>750 days before disease onset). These findings suggest that PMCA has the potential to detect vCJD prions in blood from asymptomatic carriers during the preclinical phase of the disease.

Animal models of nerve function have been subject to extensive study in order to understand and investigate methods which may improve axon regeneration and promote functional outcomes following nerve injury and repair. As the facial nerve is a cranial nerve, there is mounting evidence that cranial nerve regeneration differs from peripheral, and outcome models specifically addressing the facial nerve are required. Murine models are the most commonly utilized, with a variety of methods employed to measure the actions of whisking, eye closure, or ear movement as indicators of facial nerve regeneration. Each method of measurement is reviewed in terms of validity, strengths, limitations, and the specific outcome data provided. The authors propose that prior to choosing an outcome model, the goals and objectives of a planned study should be well defined, as various outcome measures may be useful depending on the information which is desired. The aim of this paper, therefore, is to provide the reader with a concise review which may facilitate project design., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Peripheral nerve assessment has traditionally been studied through histological and immunological staining techniques in a limited cross-sectional modality, making detailed analysis difficult. A new application of serial section electron microscopy is presented to overcome these limitations., Methods: Direct nerve repairs were performed on the posterior auricular nerve of transgenic YFP-H mice. Six weeks postoperatively the nerves were imaged using confocal fluorescent microscopy then excised and embedded in resin. Resin blocks were sequentially sectioned at 100 nm, and sections were serially imaged with an electron microscope. Images were aligned and autosegmented to allow for 3D reconstruction., Results: Basic morphometry and axonal counts were fully automated. Using full 3D reconstructions, the relationships between the axons, the Nodes of Ranvier, and Schwann cells could be fully appreciated. Interactions of individual axons with their surrounding environment could be visualized and explored in a virtual three-dimensional space., Conclusions: Serial section electron microscopy allows the detailed pathway of the regenerating axon to be visualized in a 3D virtual space in comparison to isolated individual traditional histological techniques. Fully automated histo-morphometry can now give accurate axonal counts, provide information regarding the quality of nerve regeneration, and reveal the cell-to-cell interaction at a super-resolution scale. It is possible to fully visualize and "fly-through" the nerve to help understand the behavior of a regenerating axon within its environment. This technique provides future opportunities to evaluate the effect different treatment modalities have on the neuroregenerative potential and help us understand the impact different surgical techniques have when treating nerve injuries., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Animal models for the study of facial paralysis have been well developed, but concern has arisen regarding the accuracy of eye closure and whisker movement as outcome measures due to new data regarding interconnectivity between facial nerve branches and autonomic innervation. The posterior auricular nerve (PAN) is an isolated branch of the facial nerve which has been confirmed as the sole motor innervat or of the interscutularis muscle. This study was designed to develop a model for facial nerve palsy utilizing the PAN and interscutularis muscle., Methods: A custom-made automated video capture system was built into a poly methyl methacrylate cage using a high definition monochrome digital camera and image sensor to record the animal as it drank from a water feeder. A copper floor pad and copper collar around the water feeder were connected to an electrical circuit for automatic saving of the video recording 10 s prior to and 30 s following the drinking event. A pre-operative baseline recording of ear movement during drinking was captured. Female YFP-16 mice at 6 weeks were assigned to sham (Sh, n = 5), nerve excision (Ex, n = 10), or nerve crush (Cr, n = 10) groups with all interventions performed on the right PAN. Sh mice were irrigated with 10 ml normal saline as were the Ex and Cr mice following operative intervention. In Ex mice, a 3 mm section of the PAN was sharply excised and nerve gap was confirmed with fluorescent microscopy. In Cr mice, the PAN was crushed 3 mm from the origin of the facial nerve trunk with size 5 jeweler's forceps for two periods of 20 s. Post-operative video recordings were collected on post-operative days (POD) 1, 10, 20, and 30. To determine the change in ear movement, the right ear was graphically compared to the left control side., Results: Sh animals exhibited a statistically significant reduction in ear movement at POD01 compared to other POD recordings (p < 0.05), but no significant change in right ear movement following POD05. Ex animals had a significant reduction in right ear movement at all PODs in comparison to the left ear (p < 0.05) with no significant change in right ear movement during the study period (p = 0.94). Cr animals showed a significant reduction in right ear movement compared to the left at POD01, POD10, and POD20 (p < 0.05). At POD30, there was no significant difference between ear movement on either side (p = 0.35). There was a significant change in right ear movement during the data collection period (p < 0.05)., Conclusion: The results show that significant differences were demonstrated between the experimental groups and that significant changes within the crush group were identifiable making this an acceptable model to develop as an accurate outcome measure following rodent facial nerve surgery., (Crown Copyright © 2019. Published by Elsevier GmbH. All rights reserved.)

Background: Recent studies suggest that purified omega-3 fatty acids may attenuate acute inflammation and hasten the transition to healing. In this study, we tested the hypothesis that pretreatment with omega-3-rich fish oil (FO) would promote resolution of peritoneal inflammation through production of specific lipid mediators., Methods: C57/BL6 mice were given a daily 200-μL oral gavage of saline (CTL) or FO (1.0-1.5 g/kg/d docosahexaenoic acid and 1.3-2.0 g/kg/d eicosapentaenoic acid) for 7 d before chemical peritonitis was induced with thioglycollate. Peritoneal lavage fluid was collected before induction and at days 2 and 4 after peritonitis onset. Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), Resolvin D1 (RvD1), and the composition of immune cell populations were examined in peritoneal lavage exudates. Cells harvested from the peritoneum were assessed for macrophage differentiation markers, phagocytosis, and lipopolysaccharide-induced cytokine secretion profiles (interleukin [IL]-6, IL-10, IL-1β, TNFα)., Results: The ratio of RvD1 to pro-inflammatory PGE2 and LTB4 was increased in the peritoneal cavity of FO-supplemented animals. FO induced a decrease in the number of monocytes in the lavage fluid, with no change in the number of macrophages, neutrophils, or lymphocytes. Macrophage phagocytosis and M1/M2 messenger RNA markers were unchanged by FO with the exception of decreased PPARγ expression. FO increased ex vivo TNFα secretion after stimulation with lipopolysaccharide., Conclusions: Our findings provide evidence that nutraceutically relevant doses of FO supplements given before and during chemical peritonitis shift the balance of lipid mediators towards a proresolution, anti-inflammatory state without drastically altering the number or phenotype of local innate immune cell populations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We describe a fast activity-dependent homeostatic regulation of intrinsic excitability of identified neurons in mouse dorsal striatum, the striatal output neurons. It can be induced by brief bursts of activity, is expressed on a time scale of seconds, limits repetitive firing, and can convert regular firing patterns to irregular ones. We show it is due to progressive recruitment of the KCNQ2/3 channels that generate the M current. This homeostatic mechanism is significantly reduced in striatal output neurons of the R6/2 transgenic mouse model of Huntington's disease, at an age when the neurons are hyperactive in vivo and the mice begin to exhibit locomotor impairment. Furthermore, it can be rescued by bath perfusion with retigabine, a KCNQ channel activator, and chronic treatment improves locomotor performance. Thus, M-current dysfunction may contribute to the hyperactivity and network dysregulation characteristic of this neurodegenerative disease, and KCNQ2/3 channel regulation may be a target for therapeutic intervention.

Proteins of the major histocompatibility complex class I (MHCI) are known for their role in the vertebrate adaptive immune response, and are required for normal postnatal brain development and plasticity. However, it remains unknown if MHCI proteins are present in the mammalian brain before birth. Here, we show that MHCI proteins are widely expressed in the developing mouse central nervous system at mid-gestation (E9.5-10.5). MHCI is strongly expressed in several regions of the prenatal brain, including the neuroepithelium and olfactory placode. MHCI is expressed by neural progenitors at these ages, as identified by co-expression in cells positive for neuron-specific class III β-tubulin (Tuj1) or for Pax6, a marker of neural progenitors in the dorsal neuroepithelium. MHCI is also co-expressed with nestin, a marker of neural stem/progenitor cells, in olfactory placode, but the co-localization is less extensive in other regions. MHCI is detected in the small population of post-mitotic neurons that are present at this early stage of brain development, as identified by co-expression in cells positive for neuronal microtubule-associated protein-2 (MAP2). Thus MHCI protein is expressed during the earliest stages of neuronal differentiation in the mammalian brain. MHCI expression in neurons and neural progenitors at mid-gestation, prior to the maturation of the adaptive immune system, is consistent with MHCI performing non-immune functions in prenatal brain development. These results raise the possibility that disruption of the levels and/or patterns of MHCI expression in the prenatal brain could contribute to the pathogenesis of neurodevelopmental disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Liver thyronine 5'-deiodinase activity assayed in crude homogenates in the absence of dithiothreitol (DTT) is increased in rats killed by asphyxia when compared to that of animals killed by phenobarbital injection or decapitation. The addition of cyclic adenosine monophosphate leads to a consistent decrease in observed deiodinase activity, suggesting the possible involvement of this nucleotide in the regulation of this enzyme. The addition of DTT eliminates this effect and suggest a dual regulation of the enzyme by cAMP and physiological sulfhydryl compounds.

Post-mortem T3 levels have been reported to be increased in victims of SIDS. Recent animal studies suggest, however, that elevated T3 in SIDS may be a non-specific post-mortem phenomenon. Therefore, we studied the possible effects of post-mortem time on T3 levels in 10- and 20-day-old rats killed by various methods including: Sodium pentobarbital overdose, injection of KCl, cervical dislocation or asphyxia with 100% N, 95% N-5% CO2 or 100% CO2. In both age groups T3 remained unchanged or increased slightly when the animals were killed with Na Pentobarbital or KCl. Greater increases were observed when rats were killed by cervical dislocation or asphyxia (100% N, 95% N-5% CO2 or 100% CO2). T3 levels did not become elevated in asphyxiated adult rats in which the inferior vena cava was ligated immediately following death. By extension to the human infant, the results of this study support the possibility that elevated T3 levels in SIDS victims may result from post-mortem processes. However, these results also suggest that the post-mortem elevation in T3 levels may be directly related to the mode of death.

It has been suggested that pyridoxine deficiency may potentiate ethanol-induced liver injury. Our purpose was to clarify the effect of pyridoxine deficiency on ethanol-associated liver injury by comparing liver histology, serum liver enzymes, and the viability of cultured hepatocytes from pyridoxine-deficient and pyridoxine-sufficient rats that had been chronically fed ethanol-enriched diets. Our data fail to substantiate that pyridoxine-deficient animals are more susceptible to the hepatotoxic effects of ethanol than pair-fed pyridoxine-sufficient controls. Furthermore, the addition of pyridoxine to hepatocyte cultures fails to prevent in vitro cytotoxicity of added ethanol. Pyridoxine deficiency may augment ethanol-induced enhancement of hepatic urea synthesis. These data suggest that pyridoxine deficiency may contribute to the abnormal plasma amino acid profiles and nitrogen balance of chronic alcoholics, but that it does not potentiate ethanol-induced liver injury.