The Summer Bird Community in a Late-Successional Beech-Maple Forest in Ohio

Author Institution: Department of Biology, Hiram CollegeWe studied the summer bird community in an unfragmented, late-successional, 61 ha beechmaple forest at the James H. Barrow Field Station in Portage County, Ohio. Birds were surveyed by making 30 counts along either of two trails in June and July of 1992, and recording all individuals seen or heard. During the survey period, we made 958 observations of 29 species. The five most common species, acadian flycatcher (Empidonax virescens), wood thrush (Hylocichia mustelina), red-eyed vireo (yireo olivaceus), hooded warbler (Wilsonia citrina), and northern cardinal (Cardinalis cardinalis') accounted for over 50% of the observations made. Of the 15 Neotropical migrants found, seven have experienced population declines in the eastern United States between 1978 and 1987, and eight are considered to be area-sensitive. The beech-maple forest we surveyed is likely to be a regionally important natural area, for it provides breeding habitat for many declining and area-sensitive bird species that would not be consistently present in smaller, more disturbed forests

A durable gain in motor and non-motor symptoms of Parkinson’s Disease following repeated caloric vestibular stimulation: A single-case study

Objective: To gain ‘first-in-man’ evidence that repeated caloric vestibular stimulation (CVS), a non-invasive form of neuro-modulation, can induce a lasting and clinically-relevant reduction in Parkinson’s Disease (PD) symptoms. Methods: A 70yr old male, diagnosed with PD 7 years prior to study enrolment, self-administered CVS at home 2x20 minutes per day for three months using a solid-state portable device. Standardised neuropsychological assessments of motor, cognitive, affective and independent function were carried out prior to stimulation, at the start and end of the sham (month 1) and active (months 2-3) phases, and 5 months post-stimulation. Results: Relative to the pre-stimulation baseline, behavioural improvements that exceeded the minimal detectable change were observed on the EQ5D, Unified Parkinson’s Disease Rating Scale, Schwab and England scale, 2 minute walk, Timed up and go, Non-motor symptom assessment scale for PD, Montreal cognitive assessment, Hospital depression scale and Epworth sleepiness scale. The level of change exceeded the threshold for a minimal clinically important difference on all scales for which a threshold has been published. By contrast, little improvement was seen during the sham (i.e. placebo) phase. Conclusion: Caloric vestibular stimulation may offer a novel, home-based method of relieving everyday symptoms of PD, and merits further evaluative study

New Understanding of β-Cell Heterogeneity and In Situ Islet Function

Insulin-secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific subpopulations with distinct functional characteristics, developmental programs, abilities to proliferate in response to metabolic or developmental cues, and resistance to immune-mediated damage. Importantly, these subpopulations change in disease or aging, including in human disease. Although discovering new β-cell subpopulations has substantially advanced our understanding of islet biology, a point of caution is that these characteristics have often necessarily been identified in single β-cells dissociated from the islet. β-Cells in the islet show extensive communication with each other via gap junctions and with other cell types via diffusible chemical messengers. As such, how these different subpopulations contribute to in situ islet function, including during plasticity, is not well understood. We will discuss recent findings revealing functional β-cell subpopulations in the intact islet, the underlying basis for these identified subpopulations, and how these subpopulations may influence in situ islet function. Furthermore, we will discuss the outlook for emerging technologies to gain further insight into the role of subpopulations in in situ islet function.</jats:p

The MafA transcription factor becomes essential to islet β-cells soon after birth

The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB

Inhibition of 12/15-Lipoxygenase Protects Against β-Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes

Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-Lipoxygenase (12/15-LOX) is induced in β-cells and macrophages during T1D and produces proinflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling has suggested reduced promiscuity of ML351 compared with ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of proinflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced β-cell oxidative stress, and preservation of β-cell mass. In the nonobese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced β-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in insulitis. The data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of β-cell dysfunction and glycemic deterioration in models of T1D

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

N.R.J. was supported by a Diabetes UK RW and JM Collins Studentship (12/0004601). J.B. was supported by a European Foundation for the Study of Diabetes (EFSD) Albert Renold Young Scientist Fellowship and a Studienstiftung des deutschen Volkes PhD Studentship. D.T. was supported by an Advanced Grant from the European Research Commission (268795). G.A.R. was supported by Wellcome Trust Senior Investigator (WT098424AIA) and Royal Society Wolfson Research Merit Awards, and by MRC Programme (MR/J0003042/1), Biological and Biotechnology Research Council (BB/J015873/1), and Diabetes UK Project (11/0004210) grants. G.A.R. and M.W. acknowledge COST Action TD1304 Zinc-Net. D.J.H. was supported by Diabetes UK R.D. Lawrence (12/0004431), EFSD/Novo Nordisk Rising Star and Birmingham Fellowships, a Wellcome Trust Institutional Support Award, and an MRC Project Grant (MR/N00275X/1) with G.A.R. D.J.H and G.A.R. were supported by Imperial Confidence in Concept (ICiC) Grants. J.F. was supported by an MRC Programme grant (MR/L02036X/1). L.P. provided human islets through collaboration with the Diabetes Research Institute, IRCCS San Raffaele Scientific Institute (Milan), within the European islet distribution program for basic research supported by JDRF (1-RSC-2014-90-I-X). P.M. and M.B. were supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 155005 (IMIDIA), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution, and by the Italian Ministry of University and Research (PRIN 2010-2012). D.B. and E.B. provided human islets through the European Consortium for Islet Transplantation sponsored by JDRF (1-RSC-2014-100-I-X)

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504–32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer’s disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentatothalamo- motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity

Clinical phenotype and outcome of hepatitis E virus - associated neuralgic amyotrophy

Objective: To determine the clinical phenotype and outcome in hepatitis E virus–associated neuralgic amyotrophy (HEV-NA). Methods: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. Results: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12–2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. Conclusions: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted