bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity‐independent mechanism
Authors: Miyara Masatsugu , Kotake Yaichiro , Tokunaga Wataru , Sanoh Seigo , Ohta Shigeru 
Published: June 2016

AbstractParkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD‐related neurotoxin MPP+ suggest autophagy involvement in the pathogenesis of PD, the effect of MPP+ on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP+ exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP+ toxicity (2.5 and 5 mM for 24 h). In SH‐SY5Y cells, mild MPP+ exposure predominantly inhibited autophagosome degradation, whereas acute MPP+ exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP+ exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP+ exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP+ exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP+ exposure and mechanistic differences between mild and acute MPP+ toxicities. Mild MPP+ toxicity impaired autophagosome degradation through novel lysosomal acidity‐independent mechanisms. Sustained mild lysosomal damage may contribute to PD.
image
We examined the effects of MPP+ on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH‐SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP+ exposure. Mechanistic differences between acute and mild MPP+ toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson's disease.Cover Image for this issue: doi: 10.1111/jnc.13338.
Sphingosine 1‐phosphate receptor 1 is required for retinal ganglion cell survival after optic nerve trauma
Authors: Joly Sandrine , Pernet Vincent 
Published: June 2016

AbstractIn this study, we used a classical optic nerve injury model to address the function of the sphingosine 1‐phosphate (S1P)–S1P receptor (S1PR) axis in retinal ganglion cell (RGC) death and axonal growth. After lesion, the expression of S1PR1 was generally reduced in axotomized RGCs but persisted in αRGCs, a subpopulation of injury‐resistant RGCs. Silencing S1PR1 with an adeno‐associated virus serotype 2 (AAV2) containing a shRNA specific to S1PR1 (AAV2.shRNA‐S1PR1) exacerbated the loss of RGCs induced by optic nerve crush; the rate of RGC survival was decreased by more than 24% in retinae infected with AAV2.shRNA‐S1PR1 compared with AAV2.shRNA‐scrambled or AAV2.GFP control treatments. In the superior and temporal regions of the retina, cell death rose by more than ~ 35% and ~ 50%, respectively, in comparison with control groups. In the optic nerve, S1PR1 silencing markedly reduced axonal sprouting after the lesion relative to control animals. Early after optic nerve crush, 67% of αRGCs stained for osteopontin were lost in retinae infected with AAV2.shRNA‐S1PR1, whereas the number of intrinsically photosensitive RGCs expressing melanopsin, another injury‐resistant RGC type, was not affected. Moreover, retinal infection with AAV2.shRNA‐S1PR1 down‐regulated mammalian target of rapamycin pathway activation in αRGCs. Together, our results reveal that S1PR1 contributes to survival and growth mechanisms in injured RGCs by regulating the mammalian target of rapamycin pathway.
imageThe role of sphingosine 1‐phosphate receptor 1 (S1PR1) was studied in retinal ganglion cell survival and axonal growth after optic nerve injury. After axonal damage, S1PR1 expression was decreased in retinal neurons. Viral‐mediated S1PR1 down‐regulation enhanced injury‐induced cell death and reduced spontaneous axonal growth. In injury‐resistant retinal neurons, the activation of mTOR signalling was down‐regulated by silencing S1PR1, suggesting an important role for S1PR1 in neuronal growth and survival mechanisms in vivo.
Oestrogens and Progestagens: Synthesis and Action in the Brain
Authors: Rossetti M. F. , Cambiasso M. J. , Holschbach M. A. , Cabrera R. 
Published: June 2016

When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide‐induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side‐chain cleavage, 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase, cytochrome P450arom, steroid 5α‐reductase and 3α‐hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.
Background of couples undergoing non‐invasive prenatal testing in Japan
Authors: Takeda Eri , Suzumori Nobuhiro , Kumagai Kyoko , Oseto Kumiko , Ebara Takeshi , Yotsumoto Junko , Numabe Hironao , Sugiura‐Ogasawara Mayumi 
Published: June 2016

AbstractAimOur purpose was to assess the background of couples who were undergoing non‐invasive prenatal testing (NIPT) in Japan.MethodsThe characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode.ResultsCompared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35–39 years: 21.2% vs 7.5%, 40–45 years: 36.2% vs 12.6%), compared with the controls.ConclusionKnowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT.
Genetics and epigenetics in small intestinal neuroendocrine tumours
Authors: Stålberg P. , Westin G. , Thirlwell C. 
Published: June 2016

AbstractNeuroendocrine tumour of the small intestine (SI‐NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI‐NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5‐year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60–90% of SI‐NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI‐NETs but, with a frequency as low as 8%, its role as a driver in SI‐NET development may be questioned. Integrated genomewide analysis including exome and whole‐genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI‐NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI‐NETs have significant epigenetic dysregulation in 70–80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI‐NETs.
Systemic lupus erythematosus: still a challenge for physicians
Authors: Bengtsson A. A. , Rönnblom L. 
Published: June 2016

AbstractSystemic lupus erythematosus (SLE) has a complex clinical picture, and a number of defects in the immune system have been described in patients with the disease. Most organs can be involved in SLE, and in addition to the typical major organ manifestations (e.g. from kidneys and the central nervous system), early cardiovascular disease is a major determinant of prognosis. Several important findings during the last decade have increased the understanding of the mechanisms behind the disease characteristics and the underlying autoimmune process. Amongst, these are defects in the handling of apoptotic cells, increased expression of type I interferon‐regulated genes and activation of autoreactive B cells, with both the type I interferon system and the B lymphocyte stimulator (BLyS) having key roles. In addition, a large number of genes have been identified that contribute to these abnormalities. It has also become clear that certain SLE risk genes are associated with some organ manifestations, such as STAT4 with nephritis and IRF8 with myocardial infarction. Furthermore, environmental factors that can induce SLE or trigger a disease flare have been identified. As a consequence of this increased knowledge, new treatments for SLE have been developed. The most recently approved drug for SLE is belimumab, which blocks BLyS, and several new therapies and therapeutic strategies are in the pipeline for clinical application.
The use of generic medications for hepatitis C
Authors: Freeman James A. D. , Hill Andrew 
Published: June 2016

AbstractHepatitis C, hepatitis B, HIV, TB and malaria are the five major causes of infectious disease death worldwide. In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market, but, in what must be one of the greatest tragedies of modern times, these life‐saving medications are not being deployed on a mass scale. Pharmaceutical patents are gifted to private corporations by governments for the dual purposes of protecting R&D expenditure and encouraging innovation. Unfortunately the monopoly pricing power these patents provision currently lacks adequate checks and balances, is open to abuse, and is quite clearly being abused. The sort of legislative changes required to deliver on the original goals of pharmaceutical patents will take years or even decades to eventuate. Parallel importation of generic medication offers hope to the millions of patients with HCV unable to afford access to vastly overpriced originator medications. Doctors prescribing and monitoring patients taking generics can take comfort from the fact that the REDEMPTION trial results show, like the HIV generics that came before them, that HCV generics deliver robust clinical results.
Don't bet against the natal homing abilities of marine fishes
Authors: Bentzen Paul , Bradbury Ian R. 
Published: June 2016

Whether marine fishes are capable of homing to their natal areas has long been something of an enigma. For some estuarine species or sharks (which have extended nondispersal juvenile stages or are born as relatively large, fully formed juveniles), the answer is clearly ‘yes’ (Thorrold et al. ; Feldheim et al. ), but for most marine fishes, the issue is much more mysterious. Many species have free‐floating eggs, and most have pelagic, passively dispersing larvae. It is challenging to imagine how adult fish might navigate to a region of the ocean they experienced only as eggs or larvae, and easier to assume that such dispersal leads inexorably to high gene flow, and even panmixia. One way to resolve the conundrum would be to track fish from hatching to reproduction, but for marine fishes with tiny eggs and drifting larvae, this is notoriously difficult to do (Bradbury & Laurel ). In this issue of Molecular Ecology, Bonanomi et al. () use a creative approach to solve this challenge for Atlantic cod (Gadus morhua) populations that mingle in the vicinity of Greenland. They show that cod that disperse more than a 1000 km away from Iceland as eggs and larvae, then spend years growing on the far side of Greenland, while mixing with two local populations, return as adults to spawning areas near Iceland – and further, that this behaviour has remained stable over more than six decades. They manage this feat with a clever use of historical cod tracking data, modern genomic data and genetic analysis of decades‐old DNA obtained from archived materials. Their results have important implications for our view of the biocomplexity of marine fish populations, and how we should manage them.
Migraine comorbidity with cardiac, cardiovascular and cerebrovascular disease
Authors: Kato Yuji , Dodick David W , Schwedt Todd J 
Published: June 2016

AbstractMigraine has complex relationships with disorders of the heart, the cardiovasculature and the cerebrovasculature. The purpose of this review was to summarize data regarding the relationship of migraine with structural cardiac disease, cardiovascular disease and stroke. There are low‐quality and/or conflicting data regarding a possible association between migraine with patent foramen ovale and other sources of right‐to‐left shunt. If these associations exist, migraine with aura, in contrast to migraine without aura, would likely account for the comorbidity. Although low‐quality evidence suggested that patent foramen ovale closure results in improved migraine patterns, higher‐quality evidence from prospective clinical trials of patent foramen ovale closure failed to achieve their primary end‐points. There are conflicting data regarding an increased risk of cardiovascular disease in people with migraine. Overall, data suggest that migraine with aura is probably associated with an increased risk for cardiovascular disease. Consistently, studies have shown migraine with aura to be associated with an increased risk for ischemic stroke. The explanation for the comorbidity between migraine with aura and cardiovascular and cerebrovascular diseases has yet to be adequately defined. Potential causal relationships and shared underlying risk factors are discussed. Migraine with aura is associated with an increased risk for ischemic stroke. Migraine with aura might be associated with an increased risk for cardiovascular disease and an increased likelihood for structural cardiac disease, such as patent foramen ovale. Further investigations will define the existence and nature of the relationship between migraine with aura and these disorders.
Hearing loss in lateral medullary syndrome
Authors: Sato Kenichiro , Hida Ayumi , Omori Aki , Arai Noritoshi , Takeuchi Sousuke 
Published: June 2016

AbstractWe report a case of lateral medullary syndrome with hemiparesis and hearing loss. A 69‐year‐old man was diagnosed with right‐sided lateral medullary syndrome and cerebellar vermis infarction with ipsilateral hemiparesis as a result of an upper cervical lesion. On the seventh hospital day, ipsilateral hearing loss suddenly emerged. The results of auditory and vestibular tests, including auditory brainstem responses, suggested a possible lesion in the vestibulocochlear nerve. Hearing loss could be attributed to a non‐anterior inferior cerebellar artery, vertebral artery and/or posterior inferior cerebellar artery infarction. The possibility of comorbidity of hearing loss with lateral medullary syndrome in this case suggests the possible usefulness of further intensive antithrombotic therapy in cases of lateral medullary syndrome with uncommon presentations.
Genetic enhancement of oil content in potato tuber (Solanum tuberosum L.) through an integrated metabolic engineering strategy
Authors: Liu Qing , Guo Qigao , Akbar Sehrish , Zhi Yao , El Tahchy Anna , Mitchell Madeline , Li Zhongyi , Shrestha Pushkar , Vanhercke Thomas , Ral Jean‐Philippe , Liang Guolu , Wang Ming‐Bo , White Rosemary , Larkin Philip , Singh Surinder , Petrie James 
Published: June 2016

SummaryPotato tuber is a high yielding food crop known for its high levels of starch accumulation but only negligible levels of triacylglycerol (TAG). In this study, we evaluated the potential for lipid production in potato tubers by simultaneously introducing three transgenes, including WRINKLED 1 (WRI1), DIACYLGLYCEROL ACYLTRANSFERASE 1 (DGAT1) and OLEOSIN under the transcriptional control of tuber‐specific (patatin) and constitutive (CaMV‐35S) promoters. This coordinated metabolic engineering approach resulted in over a 100‐fold increase in TAG accumulation to levels up to 3.3% of tuber dry weight (DW). Phospholipids and galactolipids were also found to be significantly increased in the potato tuber. The increase of lipids in these transgenic tubers was accompanied by a significant reduction in starch content and an increase in soluble sugars. Microscopic examination revealed that starch granules in the transgenic tubers had more irregular shapes and surface indentations when compared with the relatively smooth surfaces of wild‐type starch granules. Ultrastructural examination of lipid droplets showed their close proximity to endoplasmic reticulum and mitochondria, which may indicate a dynamic interaction with these organelles during the processes of lipid biosynthesis and turnover. Increases in lipid levels were also observed in the transgenic potato leaves, likely due to the constitutive expression of DGAT1 and incomplete tuber specificity of the patatin promoter. This study represents an important proof‐of‐concept demonstration of oil increase in tubers and provides a model system to further study carbon reallocation during development of nonphotosynthetic underground storage organs.
Investigating the effect of cadmium and aluminium on growth and stress‐induced responses in the micropropagated medicinal plant Hypoxis hemerocallidea
Authors: Okem A. , Moyo M. , Stirk W. A. , Finnie J. F. , Van Staden J. 
Published: June 2016

Abstract

Hypoxis hemerocallidea is a highly utilized medicinal plant in South Africa. Its cultivation has received considerable attention in order to meet the high demand. High levels of cadmium (Cd) and aluminum (Al) in H. hemerocallidea plants sold in traditional medicinal markets was previously reported.

The present study used an in vitro propagation model to investigate the uptake of Cd and Al by H. hemerocallidea and their effect on plant growth, elemental uptake and some stress‐induced responses such as pigment, malondialdehyde (MDA), proline content and ultrastructural changes.

Shoot and root growth of plantlets exposed to Cd, Cd:Al and high concentrations of Al was significantly reduced. Highest concentrations of Cd accumulated in the corms of Cd‐treated plantlets while highest Al concentrations occurred in the leaves and roots. There was higher accumulation of Cd and Al when applied singularly compared to the Cd:Al combination treatments. Cd and Al also reduced accumulation of trace elements in micropropagted H. hemerocallidea with lowest concentrations in the Cd:Al combination treatments. Exposure to Cd, Al and Cd:Al significantly reduced the level of chlorophyll but increased the levels of carotenoids, MDA and proline. Ultrastructural changes were also observed in H. hemerocallidea exposed to Cd and Al.

All these factors contributed to the inhibition of plant growth and could potentially affect the ability of this important medicinal plant to synthesize bioactive compounds. It is thus necessary to understand heavy metal stress‐induced responses in this highly valued medicinal plant to ensure a high quality product for the consumer.
Use of formalin in intensive aquaculture: properties, application and effects on fish and water quality
Authors: Leal Joana F. , Neves Maria Graça P. M. S. , Santos Eduarda B. H. , Esteves Valdemar I. 
Published: June 2016

AbstractFormalin (aqueous solution of formaldehyde stabilized with methanol) is one of the most used disinfectants in aquaculture. It is used to eliminate infectious agents but may be responsible for negative effects on fish and water quality. This work focuses on physical–chemical properties of formalin and on its reactions and its use in intensive aquaculture and in environment. The types of treatments and the action mode of formalin are also described. The main consequences of formalin exposure to fish are damage in gills and alterations in mucous cells. Formalin also interacts with some treatments adopted in aquaculture establishments, for example biological filter, where the nitrification process seems to be strongly affected. With respect to formalin inactivation, formaldehyde (effluent) may be diluted with water or specific treatments should be conducted to decrease the concentration levels before its discharge into the environment. The common methodologies applied to aquaculture are not completely efficient on formalin removal from water, and the advanced oxidation processes may be a good alternative.