Miracle-dz/UniFAR-FTUs huggingface dataset:
SOK1 Translocates from the Golgi to the Nucleus upon Chemical Anoxia and Induces Apoptotic Cell Death*

SOK1 is a Ste20 protein kinase of the germinal center kinase (GCK) family that has been shown to be activated by oxidant stress and chemical anoxia, a cell culture model of ischemia. More recently, it has been shown to be localized to the Golgi apparatus, where it functions in a signaling pathway required for cell migration and polarization. Herein, we demonstrate that SOK1 regulates cell death after chemical anoxia, as its down-regulation by RNA interference enhances cell survival. Furthermore, expression of SOK1 elicits apoptotic cell death by activating the intrinsic pathway. We also find that a cleaved form of SOK1 translocates from the Golgi to the nucleus after chemical anoxia and that this translocation is dependent on both caspase activity and on amino acids 275-292, located immediately C-terminal to the SOK1 kinase domain. Furthermore, SOK1 entry into the nucleus is important for the cell death response since SOK1 mutants unable to enter the nucleus do not induce cell death. In summary, SOK1 is necessary to induce cell death and can induce death when overexpressed. Furthermore, SOK1 appears to play distinctly different roles in stressed versus non-stressed cells, regulating cell death in the former.
How to Bid Better for the Olympics: A Participatory Mega-Event Planning Strategy for Local Legacies

Problem, research strategy, and findings: Several cities have canceled their Olympic bids in recent years because of local protests and referenda. Bidding cities now face a new political reality as they debate whether a bid is in the best interests of local stakeholders. We present a case study of Boston's (MA) ultimately unsuccessful bid to be the U.S. city selected to host the 2024 Olympic Games. Boston 2024, a nonprofit organization, prepared 2 sequential bids. We ask whether, how, and why Boston 2024 changed its planning approach from the 1st to the 2nd bid to respond to significant protests over its failure to meaningfully involve stakeholders, identify specific legacies, and provide accurate cost details. Our findings are limited by our focus on a single case, the small number of interviewees, and the constraints of ethnographic work. Boston 2024 shifted from an elite-driven process to a more inclusive one, from making generic claims about the impact of hosting the Games to describing local legacies, and from opaque budgets to transparent ones. Boston 2024 did not involve city planners in meaningful ways or engage fully with opponents. These changes were thus not sufficient to overcome substantial local distrust and opposition. Takeaway for practice: Cities considering mega-event bids should encourage a fully participatory planning process that provides genuine local legacies and is transparent about costs and who will bear overruns. City planners would contribute significantly to bid planning that meets these objectives. Cities should also pressure Olympic organizations to make supportive changes in their selection requirements.
Incidence of vestibular schwannoma in Denmark, 1977-1995.

OBJECTIVE To establish the incidence rate of vestibular schwannomas (VS) (acoustic neuromas) in Denmark. BACKGROUND The worldwide incidence rates of VS vary from 1 to 20 cases per million population per year. METHODS The nationwide and population-based age-specific, sex-specific, and calendar year-specific incidence rates of VS in Denmark between 1977 and 1995 are presented. Information on cases of VS was obtained from the Danish Cancer Registry and a clinical database situated at the University Hospital of Gentofte. A total of 795 cases were reported during the period of the study. RESULTS The incidence rate increased from 5 cases per million population per year in 1977-1981 to 10 cases in 1992-1995; the increase was from 5 to 11 cases among women and 5 to 9 cases among men. The age-specific incidence rates show that VS is rarely diagnosed in persons under 30, but the incidence rate appears to increase among women after menopause. CONCLUSION The overall incidence rate of VS increased linearly during the study period, probably owing to the introduction of more precise diagnostic procedures, increased awareness among physicians and patients of the symptoms of VS, improved registration of benign tumors in Denmark, and the use of data from two sources.
Mandatory Sustainability Reporting in Germany: Does Size Matter?

This article studies how German firms evaluate a recent national corporate social responsibility (CSR) law based on a European Union directive and the burden they expect regarding their organizational responsibilities due to mandatory sustainability reporting. One hundred and fifty-one firms of different sizes directly or indirectly affected by the law are included in the survey and their responses empirically analyzed using two-tailed t-tests and simple linear regression. Anchoring the discussion in stakeholder theory and the small and medium-sized enterprise (SME) literature while considering large-firm idiosyncrasies, the results show differing effects on SMEs and large firms as well as firms which are directly and indirectly affected. Findings show that firm size only matters for the evaluation of the law by directly affected firms, while size does not matter in the case of indirectly affected firms. Possible moderators of this evaluation are grounded in the resource-based theory and formalization of CSR. This article contributes to the understanding of when firm size matters in the case of mandatory sustainability reporting and underlines the role of organizational resources and capabilities as well as the special position of SMEs.
Intra‐articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF‐2α

We investigated the feasibility of the intra‐articular injection of resveratrol for preventing the progression of existing cartilage degeneration in a mouse model of osteoarthritis (OA). The effects of resveratrol on the expression of silent information regulator 2 type 1 (SIRT1), hypoxia‐inducible factor‐2α (HIF‐2α) and catabolic factors in OA cartilage was explored. OA was induced in the mouse knee via destabilization of the medial meniscus (DMM). Resveratrol was injected weekly into the operated knee beginning 4 weeks after surgery. The OA phenotype was evaluated via histological and immunohistochemical analyses at 8 weeks after DMM. Western blot analysis was performed to identify whether resveratrol modulated the interleukin (IL)‐1β‐induced expression of HIF‐2α in human chondrocytes. Histologically, resveratrol treatment preserved the structural homeostasis of the articular cartilage and the subchondral bone. Following resveratrol injection, the expression of collagen type II was retained, but the expression of inducible nitric oxide synthase and matrix metalloproteinase‐13 was reduced in OA cartilage. Moreover, the administration of resveratrol significantly induced the activation of SIRT1 and the inhibition of HIF‐2α expression in mouse OA cartilage and in IL‐1β‐treated human chondrocytes. These findings indicate that the intra‐articular injection of resveratrol significantly prevents the destruction of OA cartilage by activating SIRT1 and thereby suppressing the expression of HIF‐2α and catabolic factors. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1061–1070, 2015.
Human retinol dehydrogenase 13 (RDH13) is a mitochondrial short‐chain dehydrogenase/reductase with a retinaldehyde reductase activity

Retinol dehydrogenase 13 (RDH13) is a recently identified short‐chain dehydrogenase/reductase related to microsomal retinoid oxidoreductase RDH11. In this study, we examined the distribution of RDH13 in human tissues, determined its subcellular localization and characterized the substrate and cofactor specificity of purified RDH13 in order to better understand its properties. The results of this study demonstrate that RDH13 exhibits a wide tissue distribution and, by contrast with other members of the RDH11‐like group of short‐chain dehydrogenases/reductases, is a mitochondrial rather than a microsomal protein. Protease protection assays suggest that RDH13 is localized on the outer side of the inner mitochondrial membrane. Kinetic analysis of the purified protein shows that RDH13 is catalytically active and recognizes retinoids as substrates. Similar to the microsomal RDHs, RDH11, RDH12 and RDH14, RDH13 exhibits a much lower Km value for NADPH than for NADH and has a greater catalytic efficiency in the reductive than in the oxidative direction. The localization of RDH13 at the entrance to the mitochondrial matrix suggests that it may function to protect mitochondria against oxidative stress associated with the highly reactive retinaldehyde produced from dietary β‐carotene.
Response of Hepatitis C Genotype-4 Naïve Patients to 24 Weeks of Peg-Interferon-α2b/Ribavirin or Induction-Dose Interferon-α2b/Ribavirin/Amantadine: A Non-Randomized Controlled Study

BACKGROUND AND AIM:Currently, pegylated interferon is the most effective therapy for hepatitis C but its cost is out of reach of most patients in the developing countries. The aim of this study was to assess the response rate of genotype-4 patients to 24 wks of peg-interferon-α2b (Peg-IFN-α2b) and ribavirin (RBV) or interferon-α2b (IFN-α2b) with RBV and amantadine (AMD) as an alternative option.METHODS:In a controlled study, 180 biopsy-proven naïve chronic hepatitis C patients were allocated into three groups based on their financial affordability to any of the study regimens. Group I (control) comprised 40 patients who received Peg-IFN-α2b in a flat dose of 100 μg/wk (the dose available in Egypt) plus RBV 1,000–1,200 mg per day based on body weight for 48 wks. Group II comprised 70 patients who received the same regimen for 24 wks. Group III comprised 70 patients who received induction-dose triple therapy (IDTT) in the form of IFN-α2b 3 MU once daily for the first 4 wks then reduced to TIW for 20 wks plus RBV 1,000–1,200 mg per day based on body weight and AMD 100 mg twice daily for 24 wks. Six patients from group I, eight patients from group II, and four from group III discontinued the study either due to financial limitations and/or intolerable adverse effects of the drugs.RESULTS:Intention-to-treat analysis revealed that sustained virological response (SVR) achieved in 22 (55.0%), 34 (48.6%), and 20 (28.6%) in groups I, II, and III, respectively. Adherence-to-treatment analysis (80/80/80) revealed that SVR achieved in 22 (64.7%), 34 (54.8%), and 20 (30.3%) in groups I, II, and III, respectively. In absence of eradication of hepatitis-C-virus-RNA at week 12, there was virtually no chance of achieving SVR. These data collectively may indicate that genotype 4 is “not difficult to treat” as previously reported.CONCLUSION:Response of genotype-4 patients to 24 wks of Peg-IFN-α2b/RBV did not significantly differ from 48 wks, but was significantly higher than IDTT. Although SVR achieved by IDTT is less than Peg-IFN-, yet it might provide a second option when the latter is not affordable. Early virological response should be used as a predictor to SVR to avoid unnecessary expenses in nonresponders patients.
Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases

Oxidative stress induced by inhibition of glutathione (GSH) biosynthesis with D,L‐buthionine‐S,R‐sulfoximine (BSO) causes human microglia, human astrocytes, THP‐1 cells, and U373 cells to secrete materials toxic to human neuroblastoma SH‐SY5Y cells and stimulates them to release TNF‐α, IL‐6, and nitrite ions. The effect is correlated with activation of the inflammatory pathways P38 MAP‐ kinase, Jun‐N‐terminal kinase, and NF‐KB. The effect is reduced by adding to the medium GSH or clotrimazole (CTM), an inhibitor of Ca2+‐influx through TRPM2 channels. It is also produced by inhibiting TRPM2 protein expression in microglia and astrocytes through introduction of its small inhibitory RNA (siRNA). TRPM2 mRNA is expressed by glial cells but not by SH‐SY5Y cells. BSO in the culture medium causes an almost 3‐fold increase in [Ca2+]i in microglia and astrocytes over a 24‐h period, which is reduced to half by the addition of CTM. The data strongly suggest that inhibiting intracellular GSH synthesis induces a neuroinflammatory response in human microglia and astrocytes, which is linked to Ca2+ influx through TRPM2 channels. It represents a new model for inducing neuroinflammation and suggests that increasing GSH levels in glial cells may confer neuroprotection in neurodegenerative diseases, such as Alzheimer disease, which have a prominent neuroinflammatory component. —Lee, M. , Cho, T. , Jantaratnotai, N. , Wang, Y. T. , McGeer, E. , McGeer, P. L. Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases. FASEBJ. 24, 2533–2545 (2010). www.fasebj. org
Novel high gain polarization switchable rectangular slot antenna for L-band applications

A novel high gain polarization switchable rectangular slot antenna is proposed in this paper. Antenna consists of a rectangular slot can be switched in three polarization states; left hand circular polarization (LHCP), linear polarization (LP), and right hand circular polarization (RHCP) by controlling the bias voltage of PIN diodes. The proposed antenna is fabricated on a RT/duroid 5880 substrate with a dielectric constant (εr) of 2.2 and thickness (h) of 0.787mm. Slots are etched on one side of the substrate, while the microstrip feed network is printed on the other side. A metal reflector is placed in a plane parallel to the slot surface to make radiation pattern unidirectional and hence increase the overall gain of the antenna. Measured results are well matched with the simulated ones. Measured 3dB axial ratio bandwidths for LHCP and RHCP are 125 MHz and 120 MHz, respectively. Measured gain of the antenna is around 7 dB at 1.2 GHz in all three states. Proposed antenna can be used for wireless applications such as security cameras and systems.
Influence of Different Electron Donors and Acceptors on Dehalorespiration of Tetrachloroethene byDesulfitobacterium frappieri TCE1

ABSTRACT Strain TCE1, a strictly anaerobic bacterium that can grow by reductive dechlorination of tetrachloroethene (PCE) and trichloroethene (TCE), was isolated by selective enrichment from a PCE-dechlorinating chemostat mixed culture. Strain TCE1 is a gram-positive, motile, curved rod-shaped organism that is 2 to 4 by 0.6 to 0.8 μm and has approximately six lateral flagella. The pH and temperature optima for growth are 7.2 and 35°C, respectively. On the basis of a comparative 16S rRNA sequence analysis, this bacterium was identified as a new strain of Desulfitobacterium frappieri, because it exhibited 99.7% relatedness to the D. frappieri type strain, strain PCP-1. Growth with H2, formate,l-lactate, butyrate, crotonate, or ethanol as the electron donor depends on the availability of an external electron acceptor. Pyruvate and serine can also be used fermentatively. Electron donors (except formate and H2) are oxidized to acetate and CO2. When l-lactate is the growth substrate, strain TCE1 can use the following electron acceptors: PCE and TCE (to produce cis-1,2-dichloroethene), sulfite and thiosulfate (to produce sulfide), nitrate (to produce nitrite), and fumarate (to produce succinate). Strain TCE1 is not able to reductively dechlorinate 3-chloro-4-hydroxyphenylacetate. The growth yields of the newly isolated bacterium when PCE is the electron acceptor are similar to those obtained for other dehalorespiring anaerobes (e.g.,Desulfitobacterium sp. strain PCE1 andDesulfitobacterium hafniense) and the maximum specific reductive dechlorination rates are 4 to 16 times higher (up to 1.4 μmol of chloride released · min−1 · mg of protein−1). Dechlorination of PCE and TCE is an inducible process. In PCE-limited chemostat cultures of strain TCE1, dechlorination is strongly inhibited by sulfite but not by other alternative electron acceptors, such as fumarate or nitrate.
The Methylosome, a 20S Complex Containing JBP1 and pICln, Produces Dimethylarginine-Modified Sm Proteins

ABSTRACT snRNPs, integral components of the pre-mRNA splicing machinery, consist of seven Sm proteins which assemble in the cytoplasm as a ring structure on the snRNAs U1, U2, U4, and U5. The survival motor neuron (SMN) protein, the spinal muscular atrophy disease gene product, is crucial for snRNP core particle assembly in vivo. SMN binds preferentially and directly to the symmetrical dimethylarginine (sDMA)-modified arginine- and glycine-rich (RG-rich) domains of SmD1 and SmD3. We found that the unmodified, but not the sDMA-modified, RG domains of SmD1 and SmD3 associate with a 20S methyltransferase complex, termed the methylosome, that contains the methyltransferase JBP1 and a JBP1-interacting protein, pICln. JBP1 binds SmD1 and SmD3 via their RG domains, while pICln binds the Sm domains. JBP1 produces sDMAs in the RG domain-containing Sm proteins. We further demonstrate the existence of a 6S complex that contains pICln, SmD1, and SmD3 but not JBP1. SmD3 from the methylosome, but not that from the 6S complex, can be transferred to the SMN complex in vitro. Together with previous results, these data indicate that methylation of Sm proteins by the methylosome directs Sm proteins to the SMN complex for assembly into snRNP core particles and suggest that the methylosome can regulate snRNP assembly.
De Novo Cancers Arising in Organ Transplant Recipients are Associated With Adverse Outcomes Compared With the General Population

Background. Transplant recipients are at increased risk of malignancy; however, the influence of transplantation on cancer outcomes has not been rigorously defined. The purpose of this study was to examine the influence of transplantation on the outcomes of individual cancers. Methods. De novo nonsmall cell lung cancer, colon cancer, breast cancer, prostate cancer, bladder cancer, renal cell cancer (RCC), and malignant melanoma data in 635 adult (>18 years of age) transplant recipients (from the Israel Penn International Transplant Tumor Registry) were compared with data from 1,282,984 adults in the general population (from the Surveillance, Epidemiology, and End Results database). Results. Compared with the general population, transplant patients were more likely to have early stage (AJCC stage 0–II) RCC, but more advanced (AJCC stage >II) colon cancer, breast cancer, bladder cancer, and malignant melanoma. Compared with the general population, disease-specific survival was worse in the transplant population for colon cancer (all stages), nonsmall cell lung cancer (stage II), breast cancer (stage III), prostate cancer (stage II, III, and IV), bladder cancer (stage III), and RCC (stage IV). Multivariate analyses demonstrated transplantation to be a negative risk factor for survival for each cancer studied, and transplantation and cancer stage at diagnosis to be the most profound negative survival predictors. Conclusions. These analyses indicate that, for several common cancers, transplant patients experience worse outcomes than the general population. The data also suggest that cancers in transplant recipients are more aggressive biologically at the time of diagnosis.
The origin of echocardiography: a tribute to Inge Edler.

The original description of M-mode echocardiography in 1953, by Inge Edler (1911-2001) and his physicist friend Hellmuth Hertz, marked the beginning of a new diagnostic noninvasive technique. Edler used this technique primarily for the preoperative study of mitral stenosis and diagnosis of mitral regurgitation. His work was carried forward by cardiologists all over the world, who developed Doppler, 2-dimensional, contrast, and transesophageal echocardiography. These are now standard in cardiologic examinations. Edler also influenced neurologists and obstetricians at Lund University (Sweden) to use ultrasound in their fields. For his landmark discovery, Edler is recognized as the "Father of Echocardiography. "
Public/Private Partnership Schools in New Zealand: Justifications and Context

Recent policy changes in the New Zealand educational context have introduced privatization into the system through partnership schools. Parties on all sides of the issue use a framework of economic values consisting of efficiency, equity, and liberty to frame themselves and their opposition. This holistic case study uses interviews, observations, and field evidence to explore how partnership and public schools align themselves with these values, and how public discourse frames both types of schools. Cross analysis of the different voices revealed differences in constructions concerning innovation, how best to serve struggling learners, school funding, and school evaluation. These differences fuel the debate in the public sphere. The results from this study can help guide the construction of research questions and focus the inquiries of the U.S. charter school context to the underlying economic assumptions of different stakeholders, along with directing further research in the New Zealand context.
Dynamic changes in accumbens dopamine correlate with learning during intracranial self-stimulation

Dopamine in the nucleus accumbens (NAc) is an important neurotransmitter for reward-seeking behaviors such as intracranial self-stimulation (ICSS), although its precise role remains unclear. Here, dynamic fluctuations in extracellular dopamine were measured during ICSS in the rat NAc shell with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Rats were trained to press a lever to deliver electrical stimulation to the substantia nigra (SNc)/ventral tegmental area (VTA) after the random onset of a cue that predicted reward availability. Latency to respond after cue onset significantly declined across trials, indicative of learning. Dopamine release was evoked by the stimulation but also developed across trials in a time-locked fashion to the cue. Once established, the cue-evoked dopamine transients continued to grow in amplitude, although they were variable from trial to trial. The emergence of cue-evoked dopamine correlated with a decline in electrically evoked dopamine release. Extinction of ICSS resulted in a significant decline in goal-directed behavior coupled to a significant decrease in cue-evoked phasic dopamine across trials. Subsequent reinstatement of ICSS was correlated with a return to preextinction transient amplitudes in response to the cue and reestablishment of ICSS behavior. The results show the dynamic nature of chemical signaling in the NAc during ICSS and provide new insight into the role of NAc dopamine in reward-related behaviors.