bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAA receptor β3 subunit mutation D120N causes Lennox–Gastaut syndrome in knock-in mice
Authors: Qu Shimian , Catron Mackenzie , Zhou Chengwen , Janve Vaishali , Shen Wangzhen , Howe Rachel K , Macdonald Robert L 
Published: March 2020

Abstract
The Lennox–Gastaut syndrome is a devastating early-onset epileptic encephalopathy, associated with severe behavioural abnormalities. Its pathophysiology, however, is largely unknown. A de novo mutation (c.G358A, p.D120N) in the human GABA type-A receptor β3 subunit gene (GABRB3) has been identified in a patient with Lennox–Gastaut syndrome. To determine whether the mutation causes Lennox–Gastaut syndrome in vivo in mice and to elucidate its mechanistic effects, we generated the heterozygous Gabrb3+/D120N knock-in mouse and found that it had frequent spontaneous atypical absence seizures, as well as less frequent tonic, myoclonic, atonic and generalized tonic–clonic seizures. Each of these seizure types had a unique and characteristic ictal EEG. In addition, knock-in mice displayed abnormal behaviours seen in patients with Lennox–Gastaut syndrome including impaired learning and memory, hyperactivity, impaired social interactions and increased anxiety. This Gabrb3 mutation did not alter GABA type-A receptor trafficking or expression in knock-in mice. However, cortical neurons in thalamocortical slices from knock-in mice had reduced miniature inhibitory post-synaptic current amplitude and prolonged spontaneous thalamocortical oscillations. Thus, the Gabrb3+/D120N knock-in mouse recapitulated human Lennox–Gastaut syndrome seizure types and behavioural abnormalities and was caused by impaired inhibitory GABAergic signalling in the thalamocortical loop. In addition, treatment with antiepileptic drugs and cannabinoids ameliorated atypical absence seizures in knock-in mice. This congenic knock-in mouse demonstrates that a single-point mutation in a single gene can cause development of multiple types of seizures and multiple behavioural abnormalities. The knock-in mouse will be useful for further investigation of the mechanisms of Lennox–Gastaut syndrome development and for the development of new antiepileptic drugs and treatments.
Short- and mid-term effects of covered stent implantation on extremity findings and heart failure in Parkes Weber syndrome: a case report
Authors: Acar Zeydin , Kırış Abdulkadir , Bektaş Hüseyin , Erden Tuncay 
Published: March 2020

Abstract

Background
Parkes Weber syndrome (PWS) is a congenital disease characterized by vascular malformations, such as arteriovenous fistulas (AVFs). It frequently presents with overgrowth of a lower limb and high-output heart failure. The main treatment is to close vascular malformations. Surgical excision or endovascular coil insertion was performed in a few patients with AVFs. However, vascular covered stent implantation has not been used for treating PWS.

Case summary
A 15-year-old male patient with PWS presented to our hospital because of dyspnoea and massive left upper limb swelling. After initial examination and left upper limb angiography, his symptoms and findings were attributed to the presence of high-flow large AVFs despite the presence of many coils previously inserted. We decided to implant a covered stent along the AVFs between the subclavian and axillary arteries. After stent implantation, the patient’s complaints and findings improved during the early term but they relapsed at the 6th month after percutaneous intervention.

Discussion
Here, we report for the first time the use of covered stent implantation and its short and 6 months results in a patient with PWS. Although initial improvements were noted, the clinical outcome at 6 months after stent implantation was poor. This was probably associated with the presence of widespread subtle AVFs or collateral connections among the existing AVFs. Based on our result, we propose that closure of large AVFs is not useful and more definitive interventions, such as limb amputation may be required earlier.
The membrane lipid metabolism in horticultural products suffering chilling injury
Authors: Liang Shu-min , Kuang Jian-fei , Ji Shu-juan , Chen Qin-fang , Deng Wei , Min Ting , Shan Wei , Chen Jian-ye , Lu Wang-jin 
Published: March 2020

AbstractHorticultural commodities suffer chilling injury following exposure to extremely low temperatures, which results in visible symptoms and considerable quality loss. Therefore, it is of significance to understand the mechanism of this physiological disorder and to develop effective strategies to control it. Chilling stress causes alteration in structure and function of the plasma membrane, which is assumed to be the primary event in response to cold stress. During this process, the membrane lipid metabolism plays a pivotal role in membrane fluidity and stability. In this review, we summarized the possible roles of membrane lipid metabolism in the development of chilling injury, having the potential for developing effective strategies to alleviate chilling injury in horticultural products under refrigerated storage in practice.
The Imagined Ethno-Racial Border and the Expulsion of Jews from Western Poland, 1939-41*
Authors: Service Hugo 
Published: March 2020

Abstract
Although the ‘Jewish question’ had always figured prominently in Nazi ideology and long-term objectives, the population policy to which Nazi German leaders and officials gave priority in practice in 1939–1941 was the relocation of ethnic-German ‘resettlers’ to annexed western Poland. Christopher Browning and other historians have argued that while in autumn and winter 1939 the Nazi leadership appeared to view the comprehensive removal of Jews from Germany’s ‘incorporated eastern territories’ as a high priority, because they did not prioritize it in practice, it did not happen. This article shows that this interpretation does not fully reflect events. A detailed case study of the expulsion of Jewish residents from east to west within the province of Silesia’s incorporated territory in May–June 1940 demonstrates that for Nazi German elites an ethno-racial boundary ran down the middle of the incorporated territories, north to south, and west of that boundary the comprehensive removal of Jews was prioritized in practice and very nearly realized.
Weighted Gene Coregulation Network Analysis of Promoter DNA Methylation on All-Cause Mortality in Old-Aged Birth Cohorts Finds Modules of High-Risk Associated Biomarkers
Authors: Lund Jesper B , Li Shuxia , Baumbach Jan , Christensen Kaare , Li Weilong , Mohammadnejad Afsaneh , Pattie Alison , Marioni Riccardo E , Deary Ian J , Tan Qihua 
Published: March 2020

Abstract
Overall or all-cause mortality is a key measure of health in a population. Multiple epigenome-wide association studies have been conducted on all-cause mortality with limited significant findings and low replication. To elucidate the coregulated DNA methylation patterns associated with all-cause mortality, we conducted a weighted DNA methylation coregulation network analysis on whole-blood samples of 1,425 older individuals from the Lothian Birth Cohorts of 1921 and 1936. Our network-based analysis defined coregulated DNA methylation patterns in gene promoters into clusters or modules whose correlation with all-cause mortality was assessed by survival analysis. We found two significant modules or gene clusters associated with all-cause mortality in LBC1921 based on their eigengenes; one negatively correlated (p = 8.14E-03, 698 genes) and one positively correlated (p = 4.26E-02, 1,431 genes) with the risk of death. The two modules were replicated in LBC1936 with the same directions of correlation (p = 6.35E-02 and p = 3.64E-02, respectively). Furthermore, the modules revealed 32 genes associated with all-cause mortality (FDR &lt; 0.05) linked to various diseases, including cancer and diabetes. Additionally, we performed pathway analysis and found 22 pathways (FDR &lt; 0.05), including a pathway for taste transduction, which has been shown to be associated with poor prognosis in acutely hospitalized patients, and several pathways were linked to different types of cancer. The results from our network analysis show that DNA methylation of multiple genes could have been coregulated in an association with the overall risk of death. The identified epigenetic markers might help with our understanding of the molecular basis of all-cause mortality and general health.
Neuronal Aquaporin 1 Inhibits Amyloidogenesis by Suppressing the Interaction Between Beta-Secretase and Amyloid Precursor Protein
Authors: Park Jinsu , Madan Meenu , Chigurupati Srinivasulu , Baek Seung Hyun , Cho Yoonsuk , Mughal Mohamed R , Yu Amin , Chan Sic L , Pattisapu Jogi V , Mattson Mark P , Jo Dong-Gyu 
Published: March 2020

Abstract
The accumulation of amyloid-β (Aβ) is a characteristic event in the pathogenesis of Alzheimer’s disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aβ or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of β- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced β-secretase (BACE1)-mediated cleavage of APP and reduced Aβ production without altering the nonamyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aβ production. Immunoprecipitation experiments showed that AQP1 decreased the association of BACE1 with APP. Analysis of a human database showed that the amount of Aβ decreases as the expression of AQP1 increases. These results suggest that the upregulation of AQP1 is an adaptive response of neurons to stress that reduces Aβ production by inhibiting the binding between BACE1 and APP.
Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study
Authors: Huneke Nathan T M , Broulidakis M John , Darekar Angela , Baldwin David S , Garner Matthew 
Published: March 2020

AbstractBackgroundThe 7.5% CO2 inhalational model can be used to explore potential treatments for generalized anxiety disorder. However, it is unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to anxiogenic response in this model.MethodsA total of 13 healthy volunteers underwent functional magnetic resonance imaging during a passive emotional face perception task. We explored task-evoked functional connectivity in the potential threat system through generalized psychophysiological interaction analysis. Within 7 days, these participants underwent prolonged 7.5% CO2 inhalation, and results from the generalized psychophysiological interaction analysis were correlated with CO2 outcome measures.ResultsFunctional connectivity between ventromedial prefrontal cortex and right amygdala positively correlated with heart rate and subjective anxiety, while connectivity between midcingulate cortex and left amygdala negatively correlated with anxiety during CO2 challenge.ConclusionsResponse to CO2 challenge correlated with task-evoked functional connectivity in the potential threat system. Further studies should assess whether this translates into clinical populations.
Prosecuting the Nexus between Terrorism, Conflict-related Sexual Violence and Trafficking in Human Beings before National Legal Mechanisms
Authors: de Brouwer Anne-Marie , de Volder Eefje , Paulussen Christophe 
Published: March 2020

Abstract
United Nations (UN) Security Council Resolution 2331 (2016) recognizes that ‘acts of sexual and gender-based violence, including when associated to trafficking in persons, are known to be part of the strategic objectives and ideology of certain terrorist groups, used as a tactic of terrorism and an instrument to increase their finances and their power through recruitment and the destruction of communities’. In the same resolution, the Council noted that such trafficking, particularly of women and girls, ‘remains a critical component of the financial flows to certain terrorist groups’ and is ‘used by these groups as a driver for recruitment’. Boko Haram and Al-Shabaab are among the main terrorist groups that have used human trafficking (including for sexual exploitation) and conflict-related sexual violence as tactics of terrorism, or ‘sexual terrorism’. This article will: (i) explain the nexus between these three crimes; (ii) focus on its different manifestations in the context of these terrorist organizations; and (iii) reflect on the possibilities for national criminal prosecution. To assist in the fight against impunity and increase accountability, this article provides suggestions to facilitate the successful prosecution of sexual terrorism in a more survivor-centric way.
Distribution and diversity of squirrels on university and college campuses of the United States and Canada
Authors: Peplinski Joy , Brown Joel S 
Published: March 2020

Abstract
Squirrels on North American college and university campuses have been the subject of much animated conversation in informal venues, but a systematic assessment of their distribution across this habitat type has not been undertaken until now. We collected reports of squirrel species’ presence and absence from faculty experts at 536 campuses in Canada and the continental United States, and found that squirrels are nearly ubiquitous on campuses (95% had at least one species, and 40% had three or more), but that only a select few species are common campus residents. Foremost among these is the eastern gray squirrel (Sciurus carolinensis—on 62% of surveyed campuses), followed by the eastern fox squirrel (Sciurus niger), eastern chipmunk (Tamias striatus), North American red squirrel (Tamiasciurus hudsonicus), and woodchuck (Marmota monax). Eastern gray and fox squirrels partition campuses with one another, both in their shared native/core range and on the West Coast. While these invasive eastern species are present on campuses on the West Coast, notably, contingency analysis did not provide evidence that they are the primary factor discouraging western gray squirrels (Sciurus griseus) from using these habitats. The inventory and analyses presented here can provide a basis for longitudinal studies both within and across campuses and may be productively combined with initiatives that involve students in research.
The assembly of plant–patch networks in Mediterranean alpine grasslands
Authors: Pescador David S , Iriondo José María , Losapio Gianalberto , Escudero Adrián 
Published: March 2020

AbstractAimsHarsh environmental conditions in alpine ecosystems shape vegetation structure into patches, where many different plant species cluster and grow together. Yet, which factors are important for the structure and dynamics of such plant–patch networks remains poorly understood. We aim to assess which and how environmental and biotic factors predict the assembly of plant–patch networks along a mountain range.MethodsWe examined the distribution of plant species in more than 5500 vegetation patches in 37 Mediterranean alpine grasslands distributed along a 500 m altitudinal gradient (National Park of Sierra Guadarrama, Spain). We established a plant–patch network for each grassland community and analyzed how nestedness and modularity vary with environmental (altitude, insolation and soil conditions) and biotic factors (number of species per plot, mean patch area and total pasture area).Important FindingsPlant–patch networks showed consistent, non-random patterns characterized by a nested, but not modular, structure, which suggests that positive associations among co-occurring specialists promote their growth within patches as subsets of a pool with more generalist species. Both nestedness and modularity of plant–patch networks varied among grasslands. Specifically, nestedness decreased with increasing species per plot and increased with mean patch area, while it was independent of environmental variables; modularity increased with increasing pasture area and species per plot. The negative relationship between species per plot and nested patterns may be linked to the restricted number of species that can coexist within the same patch at a given size. Moreover, the positive relationship between patch size and nestedness indicates that the growth of rare plant species within vegetation patches occupied by more abundant species is facilitated in bigger rather than smaller patches. Furthermore, these results indicate that the nested assembly of vegetation patches may be independent of abiotic conditions. These findings suggest that large and unfragmented vegetation patches are fundamental for the maintenance of plant diversity in alpine grasslands. Looking at species distribution at fine spatial scales may shed new light on the biotic processes underlying plant network assembly and provide novel ways for conserving biodiversity.
Preliminary study on radiosensitivity to carbon ions in human breast cancer
Authors: Zhang Qiuning , Kong Yarong , Yang Zhen , Liu Yang , Liu Ruifeng , Geng Yichao , Luo Hongtao , Zhang Hong , Li Hongyan , Feng Shuangwu , Wang Xiaohu 
Published: March 2020

AbstractThe aim of the study was to investigate the various effects of high linear energy transfer (LET) carbon ion (12C6+) and low LET X-ray radiation on MDA-MB-231 and MCF-7 human breast cancer cells and to explore the underlying mechanisms of radiation sensitivity. Cell proliferation, cell colony formation, cell cycle distribution, cell apoptosis and protein expression levels [double-strand break marker γ-H2AX, cell cycle-related protein cyclin B1, apoptosis-related proteins Bax and Bcl-2, and the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase B1 (p70S6K) pathway] were detected after irradiation with carbon ions or X-rays at doses of 0, 2, 4 and 8 Gy. Our results showed that the inhibition of cell proliferation and cell colony formation and the induction of G2/M phase arrest, DNA lesions and cell apoptosis/necrosis elicited by carbon ion irradiation were more potent than the effects elicited by X-ray radiation at the same dose. Simultaneously, compared with X-ray radiation, carbon ion radiation induced a marked increase in Bax and prominent decreases in cyclin B1 and Bcl-2 in a dose-dependent manner. Furthermore, the Akt/mTOR/p70S6K pathway was significantly inhibited by carbon ion radiation in both breast cancer cell lines. These results indicate that carbon ion radiation kills MDA-MB-231 and MCF-7 breast cancer cells more effectively than X-ray radiation, which might result from the inhibition of the Akt/mTOR/p70S6K pathway.
A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance
Authors: Burrell Justin C , Browne Kevin D , Dutton John L , Laimo Franco A , Das Suradip , Brown Daniel P , Roberts Sanford , Petrov Dmitriy , Ali Zarina , Ledebur Harry C , Rosen Joseph M , Kaplan Hilton M , Wolf John A , Smith Douglas H , Chen H Isaac , Cullen D Kacy 
Published: March 2020

Abstract

BACKGROUND
Millions of Americans experience residual deficits from traumatic peripheral nerve injury (PNI). Despite advancements in surgical technique, repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with slow rates of axonal regeneration. Novel surgical solutions require valid preclinical models that adequately replicate the key challenges of clinical PNI.

OBJECTIVE
To develop a preclinical model of PNI in swine that addresses 2 challenging, clinically relevant PNI scenarios: long segmental defects (≥5 cm) and ultra-long regenerative distances (20-27 cm). Thus, we aim to demonstrate that a porcine model of major PNI is suitable as a potential framework to evaluate novel regenerative strategies prior to clinical deployment.

METHODS
A 5-cm-long common peroneal nerve or deep peroneal nerve injury was repaired using a saphenous nerve or sural nerve autograft, respectively. Histological and electrophysiological assessments were performed at 9 to 12 mo post repair to evaluate nerve regeneration and functional recovery. Relevant anatomy, surgical approach, and functional/histological outcomes were characterized for both repair techniques.

RESULTS
Axons regenerated across the repair zone and were identified in the distal stump. Electrophysiological recordings confirmed these findings and suggested regenerating axons reinnervated target muscles.

CONCLUSION
The models presented herein provide opportunities to investigate peripheral nerve regeneration using different nerves tailored for specific mechanisms of interest, such as nerve modality (motor, sensory, and mixed fiber composition), injury length (short/long gap), and total regenerative distance (proximal/distal injury).
Novel Diagnostic Methods and Posttreatment Clinical Phenotypes Among Intracranial Germ Cell Tumors
Authors: Takami Hirokazu , Perry Avital , Graffeo Christopher S , Giannini Caterina , Daniels David J 
Published: March 2020

Abstract

BACKGROUND
Central nervous system (CNS) germ cell tumors (GCT) are rare and complex pediatric neoplasms, the optimal management of which remains an area of active investigation.

OBJECTIVE
To present an updated cohort study, with particular attention to novel diagnostic methods and posttreatment clinical phenotypes.

METHODS
A single-institution cohort study of 80 primary, neurosurgically managed, CNS GCTs was conducted at Mayo Clinic, 1988-2017.

RESULTS
Postchemotherapy resection (eg, second-look surgery) was frequently required (27.0%), especially after adjuvant therapies for nongerminomatous GCTs (NGGCTs; 14 of 28 cases, excluding mature teratoma) and significantly associated with pineal lesions, as compared to neurohypophyseal or bifocal lesions (43.6% vs 5.9% vs 6.7%, P = .004), a finding that retained statistical significance after adjusting for index extent of resection and histology (P = .04). Essentially every NGGCT case underwent at least 1 craniotomy, either on presentation, as second-look surgery, or following local recurrence. Mature teratomatous tissue was highly incident in second-look specimens (84.2%), even among lesions initially diagnosed as germinomas. Pretreatment cerebrospinal fluid (CSF) cell fraction analysis demonstrated an association between single lesions and neutrophil predominance, whereas nongerminomatous GCTs were associated with increased monocyte fractions.

CONCLUSION
CNS GCTs are clinically heterogeneous lesions, resulting in numerous opportunities for improved understanding and clinical management via novel diagnostic and therapeutic protocols. Samples from second-look surgeries for recurrent germinomas frequently demonstrate teratomatous tissue, suggesting possible underdiagnosis of mixed GCTs—particularly among pineal lesions. GCT subtypes demonstrate differential cell fraction distributions on CSF analysis, a novel and perhaps diagnostically helpful finding that requires validation in external cohorts.