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Glioma is the most common malignancy of the nervous system with high rates of recurrence and mortality, even after surgery. The 5‐year survival rate is only about 5%. NEK8 is involved in multiple biological processes in a variety of cancers; however, its role in glioma is still not clear. In the current study, we evaluated the prognostic value of NEK8, as well as its role in the pathogenesis of glioma. Using a bioinformatics approach and RNA‐seq data from public databases, we found that NEK8 expression is elevated in glioma tissues; we further verified this result by RT‐PCR, Western blotting and immunochemistry using clinical samples. Functional enrichment analyses of genes with correlated expression indicated that elevated NEK8 expression is associated with increased immune cell infiltration in glioma and may affect the tumour microenvironment via the regulation of DNA damage/repair. Survival analyses revealed that high levels of NEK8 are associated with a poorer prognosis; higher WHO grade, IDH status, 1p/19q codeletion, age and NEK8 were identified as an independent prognostic factor. These findings support the crucial role of NEK8 in the progression of glioma via effects on immune cell infiltration and suggest that it is a new prognostic biomarker.

Residual sulfate (SO42- ) in precursor Ni0.8 Co0.15 Mn0.05 (OH)2 (pre-NCM) is commonly regarded as being harmful to Li[Ni0.8 Co0.15 Mn0.05 ]O2 (NCM) performance, leading to significant performance losses and also hampering the electrode fabrication. Therefore, manufacturers try their best to lower sulfate contents in pre-NCM. However, how the sulfate affects the cathode materials is not systematically studied. To address these issues, NCM was synthesized with different amounts of intentionally added sulfate (NH4 )2 SO4 in pre-NCM. It was demonstrated that anionic SO42- doped in NCM could influence the grain size in sintering process and stabilize the layer structure during the charge-discharge process at a certain doping amount. The first-principles calculations suggested that the SO42- doped in the transition metal layer could effectively facilitate Li+ diffusion in the lattice. SO42- doping could reduce the energy barrier for Li+ migration and then suppress drastic contraction of the c axis during cycling. The phase transition of H2 to H3 caused by c axis contraction was suppressed and the cycling performance was enhanced. The capacity retention could reach 80.9 (0.2 C) and 80.4 % (1 C) after 380 and 240 cycles in coin cells, respectively. These findings illustrate that a certain amount of sulfate could be beneficial to NCM cathodes.

It is increasingly accepted that early cognitive impairment in Alzheimer's disease results in considerable part from synaptic dysfunction caused by the accumulation of a range of oligomeric assemblies of amyloid β-protein (Aβ). Most studies have used synthetic Aβ peptides to explore the mechanisms of memory deficits in rodent models, but recent work suggests that Aβ assemblies isolated from human (AD) brain tissue are far more potent and disease-relevant. Although reductionist experiments show Aβ oligomers to impair synaptic plasticity and neuronal viability, the responsible mechanisms are only partly understood. Glutamatergic receptors, GABAergic receptors, nicotinic receptors, insulin receptors, the cellular prion protein, inflammatory mediators, and diverse signaling pathways have all been suggested. Studies using AD brain-derived soluble Aβ oligomers suggest that only certain bioactive forms (principally small, diffusible oligomers) can disrupt synaptic plasticity, including by binding to plasma membranes and changing excitatory-inhibitory balance, perturbing mGluR, PrP, and other neuronal surface proteins, down-regulating glutamate transporters, causing glutamate spillover, and activating extrasynaptic GluN2B-containing NMDA receptors. We synthesize these emerging data into a mechanistic hypothesis for synaptic failure in Alzheimer's disease that can be modified as new knowledge is added and specific therapeutics are developed.

Background Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of normal 24-hour BP dipping pattern in chronic kidney disease (CKD) patients is not known. Aims To investigate the effect of evening dosing regimen of antihypertensive drugs on blood pressure patterns to CKD patients with hypertension. Methods We did a systematic review by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Results Five randomized controlled trials (RCTs) and one comparative study, including 3732 patients met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio [RR], 95% CI, [0.43, 0.84]). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD −3.17 mmHg, 95% CI, [−5.41, −0.94]), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD −1.37 mmHg. 95% CI. [−2.05, −0.69]) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI, [0.10, 2.19]) in patients assigned to evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. Conclusion This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients.

The early initiation of renal replacement therapy has been recommended for patients with acute renal failure by some studies, but its effects on mortality and renal recovery are unknown. We conducted an updated meta-analysis to provide quantitative evaluations of the association between the early initiation of renal replacement therapy and mortality for patients with acute kidney injury. After applying inclusion/exclusion criteria, 51 studies, including 10 randomized controlled trials, with a total of 8179 patients were analyzed. Analysis of the included trials showed that patients receiving early renal replacement therapy had a 25% reduction in all-cause mortality compared to those receiving late renal replacement therapy (risk ratio [RR] 0.75, 95% CI [0.69, 0.82]). We also noted a 30% increase in renal recovery (RR 1.30, 95% CI [1.07, 1.56]), a reduction in hospitalization of 5.84 days (mean difference [MD], 95% CI [–10.27, –1.41]) and a reduction in the duration of mechanical ventilation of 2.33 days (MD, 95% CI [–3.40, –1.26]) in patients assigned to early renal replacement therapy. The early initiation of renal replacement therapy was associated with a decreased risk of all-cause mortality compared with the late initiation of RRT in patients with acute kidney injury. These findings should be interpreted with caution given the heterogeneity between studies. Further studies are needed to identify the causes of mortality and to assess whether mortality differs by dialysis dose.

The histopathological hallmark of Alzheimer's disease (AD) is the aggregation and accumulation of the amyloid beta peptide (Aβ) into misfolded oligomers and fibrils. Here we examine the biophysical properties of a protective Aβ variant against AD, A2T, and a causative mutation, A2T, along with the wild type (WT) peptide. The main finding here is that the A2V native monomer is more stable than both A2T and WT, and this manifests itself in different biophysical behaviors: the kinetics of aggregation, the initial monomer conversion to an aggregation prone state (primary nucleation), the abundances of oligomers, and extended conformations. Aggregation reaction modeling of the conversion kinetics from native monomers to fibrils predicts the enhanced stability of the A2V monomer, while ion mobility spectrometry-mass spectrometry measures this directly confirming earlier predictions. Additionally, unique morphologies of the A2T aggregates are observed using atomic force microscopy, providing a basis for the reduction in long term potentiation inhibition of hippocampal cells for A2T compared with A2V and the wild type (WT) peptide. The stability difference of the A2V monomer and the difference in aggregate morphology for A2T (both compared with WT) are offered as alternate explanations for their pathological effects.

Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine expressed throughout the CNS. Previous studies demonstrated that TGF-β1 contributes to maintain neuronal survival, but mechanistically this effect is not well understood. We generated a CNS-specific TGF-β1-deficient mouse model to investigate the functional consequences of TGF-β1-deficiency in the adult mouse brain. We found that depletion of TGF-β1 in the CNS resulted in a loss of the astrocyte glutamate transporter (GluT) proteins GLT-1 (EAAT2) and GLAST (EAAT1) and decreased glutamate uptake in the mouse hippocampus. Treatment with TGF-β1 induced the expression of GLAST and GLT-1 in cultured astrocytes and enhanced astroglial glutamate uptake. Similar to GLT-1-deficient mice, CNS-TGF-β1-deficient mice had reduced brain weight and neuronal loss in the CA1 hippocampal region. CNS-TGF-β1-deficient mice showed GluN2B-dependent aberrant synaptic plasticity in the CA1 area of the hippocampus similar to the glutamate transport inhibitor DL-TBOA and these mice were highly sensitive to excitotoxic injury. In addition, hippocampal neurons from TGF-β1-deficient mice had elevated GluN2B-mediated calcium signals in response to extrasynaptic glutamate receptor stimulation, whereas cells treated with TGF-β1 exhibited reduced GluN2B-mediated calcium signals. In summary, our study demonstrates a previously unrecognized function of TGF-β1 in the CNS to control extracellular glutamate homeostasis and GluN2B-mediated calcium responses in the mouse hippocampus.

Manuscript Type: Empirical Research Question/Issue: Effective corporate governance requires accurate and reliable financial information. Historically, each nation has developed and pursued its own financial standards; however, as financial markets consolidate into a global market, there is a need for a common set of financial standards. As a result, there is a movement towards harmonization of international financial reporting standards (IFRS) throughout the global economy. While there has been considerable research on the effects of IFRS adoption, there has been relatively little systematic study as to the antecedents of IFRS adoption. Consequently, this study seeks to understand why some economies have quickly embraced IFRS standards while others partially adopt IFRS and still others continue to resist. Research Findings/Results: After controlling for market capitalization and GDP growth, we find that foreign aid, import penetration, and level of education achieved within a national economy are all predictive of the degree to which IFRS standards are adopted across 132 developing, transitional and developed economies. Theoretical/Academic Implications: We found that all three forms of isomorphic pressures (i.e., coercive, mimetic, and normative) are predictive of IFRS adoption. Consequently, institutional theory with its emphasis on legitimacy-seeking by social actors was relatively well supported by our data. This suggests that the IFRS adoption process is driven more by social legitimization pressures, than it is by economic logic. Practitioner/Policy Implications: For policy makers, our findings suggest that the institutional pressures within an economy are the key drivers of IFRS adoption. Consequently, policy makers should seek to influence institutional pressures that thwart and/or enhance adoption of IFRS. For executives of multinational firms, our findings provide insights that can help to explain and predict future IFRS adoption within economies where their foreign subsidiaries operate. This ability could be useful for creating competitive advantages for foreign subsidiaries where IFRS adoption was resisted, or avoiding competitive disadvantages for foreign subsidiaries unfamiliar with IFRS standards.

C orporate governance has become an important issue for Chinese and Indian firms as they increasingly interact with regulators and investors from developed markets. For instance, tapping into global capital markets to raise funds to finance their domestic and international growth requires firms from China and India to demonstrate strong corporate governance credentials, so that investors do not discount their stock (LaPorta, Lopez-de-Silanes, Shleifer, & Vishny, 2000). The swift action of Chinese and Indian authorities in response to recent corporate scandals – such as the one at Satyam Computers – reveals that even governments in emerging countries such as China and India see the need to promote good corporate governance to ensure the inflow of capital and the outflow of products. Furthermore, understanding corporate governance standards and issues in China and India is also important to executives of foreign multinationals doing business in these two countries. As concerns about corporate governance gains ascendancy in corporate board rooms and offices of policy makers, business scholars’ interest in these issues have also grown significantly, as evidenced by the number of publications on the topic (e.g., Rajagopalan & Zhang, 2008). It is this growing importance of corporate governance to the next phase of development of the Chinese and Indian economies that inspired William Q. Judge, Editor-in-Chief, and us to put together a conference and special issue on the topic for this journal.

Manuscript Type: Empirical Research Question/Issue: We study why some countries trade more than others by examining the effect of governance environment on trade flows between countries. We argue that countries with highly rule-based governance environments are relatively easy to trade with their transparent regulations and fair rules. In contrast, countries with highly relation-based governance environments are more difficult and/or more costly to trade with and therefore tend to have smaller trade flows. Research Findings/Results: Examining trade patterns among 44 countries representing 89 per cent of world trade, we find that overall, rule-based countries trade more than relation-based countries. Countries with a large gap in governance environments tend to trade less. A positive effect on trade flows exist between two highly rule-based countries, but not between two highly relation-based countries. Any trade relationship involving a relation-based country negatively affects trade flows. Theoretical Implications: This study refines and extends institutional theory and contributes to both governance and trade literatures by distinguishing two governance environments and how they affect trade flows between countries. Practical Implications: In addition to trade policies, governments must pay attention to the governance environment to evaluate their own and their trading partners' trading environment. When selecting trading partners, a firm needs to consider the prospective trading partner's characteristics (such as reputation, resources, and so forth), the trade policies of the partner's country, and the governance environment of that country.

Alzheimer's disease starts as an almost imperceptible malady, first observed clinically as a mild memory problem. Accumulating genetic and biochemical data have suggested that amyloid beta-protein (Abeta) plays an important role in this memory loss, and Abeta has been shown to suppress long-term potentiation (LTP), a cellular model for memory and learning. Here we show that a very brief (3 min) swimming, twice daily for 2 weeks, rescues LTP inhibition in the CA1 region of hippocampal slices caused by Abeta(42) or Abeta(40) carrying the Arctic mutation using a theta burst stimulation (TBS) protocol. Whereas the input-output curve was not affected, the paired-pulse ratio was reduced in mice receiving our repeated swimming protocol, suggesting a possible involvement of presynaptic facilitation. Similar to swimming, Abeta's inhibition of LTP could be rescued with the adenylyl cyclase, forskolin. Interestingly, this swimming protocol produced conditions in which a weak-TBS could invoke LTP not observed in naive mice, which again was mimicked by forskolin. In contrast, the protein kinase A (PKA) inhibitor, H89, blocked both the forskolin and swimming potentiation of LTP; these data implicate cAMP/PKA signaling in the protective effect of swimming and mediating Abeta' detrimental effects. Our data add a new simple behavior paradigm that shows the importance of an environmental factor in reversing the pathophysiological effects of Abeta, and suggest new therapeutic avenues.

Cholinergic mechanisms are critical for the generation of hippocampal theta rhythm. Cholinergic innervation of the hippocampus originates from the medial septum (MS) and cholinergic receptors are expressed in both the MS and hippocampus. In this study, we compared the effects of the muscarinic receptor antagonist atropine in the MS and the hippocampus on theta generation. Hippocampal theta rhythm was elicited by electrical stimulation of the pontine reticular formation using series of stimuli with varying intensities. Atropine was administered either systemically (50 mg/kg i.p.) or locally in the MS (microdialysis; 25 and 75 mM for 30 or 90 min) or in the hippocampus on one side (microinjection; 20 or 40 ug). The relative power at the peak theta frequency was calculated and averaged over episodes of low-intensity and high-intensity stimulations. We found that atropine drastically reduced theta rhythmic synchronization when injected in either location. After MS administration of atropine, however, high-frequency theta elicited by high-intensity stimuli was more resistant (58% and 67% decrease after 25 mM and 75 mM atropine, respectively) than slow theta elicited by low-intensity stimuli (86% and 91% decrease). There was no significant difference between the powers of the two oscillations after hippocampal injections (70-75% decrease). We conclude that the theta suppressing effect of atropine involves both hippocampal and septal mechanisms and that low-frequency theta as compared with fast theta rhythm is more sensitive to muscarinic acetylcholine receptor antagonism in the MS but not in the hippocampus.

Background Accumulating evidence suggests that insulin-like growth factor 1 (IGF1) plays an important role in Parkinson's disease (PD) pathogenesis. However, it is not clear if IGF1 polymorphism contributes to PD risk. Methods We performed a case-control study in a Han Chinese population that included 512 sporadic PD cases and 535 matched controls. All participants were genotyped for rs972936 using the Sequenom MassARRAY iPLEX platform. Serum IGF1 levels of 61 de novo, drug-naive PD patients, and 55 age- and sex-matched controls were also measured by enzyme-linked immunosorbent assay (ELISA). Results Genotype frequency of rs972936-CC was significantly associated with increased PD risk (P = 0.009), especially in males (P = 0.024) and late-onset patients (P = 0.013). Serum IGF1 levels were significantly increased in de novo, drug-naive PD patients compared with controls (P = 0.036), but were not correlated with motor dysfunction in PD patients (P = 0.220). Conclusions Our study shows that rs972936 polymorphism may increase susceptibility to PD, especially in males and late-onset patients. Further, high serum IGF1 levels may be a potential diagnostic biomarker for PD in the Han Chinese population, but does not correlate with more severe motor dysfunction.

Manuscript Type Perspective Research Question/Issue Relation-based governance has helped China to achieve rapid economic growth in its early stage; however, continuing to rely on it may hinder China's further development. The research question is: given China's cultural heritage and other institutional settings, will China be able to transition from relation-based to rule-based governance? Research Findings/Insights I discuss this question based on theoretical and empirical evidence and conclude that, first, from cost/benefit and social justice perspectives, China must complete the transition; second, cultural heritage is not the main obstacle to the transition, for the main obstacle is the powerful political forces that have been deeply entrenched in and benefited from the relation-based system. Theoretical/Academic Implications I distinguish between the governance environment at the national level and the governance choice at the organizational and individual levels. The governance environment - the set of dominant political, economic, social, and cultural institutions - facilitates and constrains the choice of the mode of governance (e.g., rule-based versus relation-based). Practitioner/Policy Implications Chinese government officials must realize the inevitability of the transition and the dire consequences of not completing it and take initiative to pursue the transition peacefully. For businesses, they must realize that the relation-based way may be in decline and must be prepared to embrace the rule-based way.