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Managing IP recognizes 33 Dentons' Intellectual Property lawyers as 2020/21 IP Stars

The 2020/ 21 edition of IP Stars, the leading specialist guide to IP firms and practitioners worldwide developed by Managing IP, has recognized 33 of Dentons’ global Intellectual Property practitioners for their outstanding experience in contentious and non-contentious IP advice in the areas of trade mark and patent work. 



  • Intellectual Property and Technology
  • Intellectual Property and Technology in Australia
  • Intellectual Property and Technology in Colombia
  • Intellectual Property and Technology in Costa Rica
  • Intellectual Property and Technology in Europe
  • Intellectual Property and Technology in Germany
  • Intellectual Property and Technology in New Zealand
  • Intellectual Property and Technology in Russia
  • CIS and the Caucasus
  • Intellectual Property and Technology in Singapore
  • Intellectual Property and Technology in the United Kingdom
  • Intellectual Property and Technology in Italy
  • Global presence
  • Australasia
  • Australia
  • New Zealand
  • Canada
  • Central and Eastern Europe
  • Europe
  • Germany
  • Italy
  • Latin America and the Caribbean
  • Mexico
  • Costa Rica
  • Russia
  • CIS and the Caucasus
  • United Kingdom
  • United States

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Affluent Indians over-invest in property

Desi billionaires hold 44 per cent of their wealth in property, while the global average is 24 per cent. From Africa to America, the rich world-over have their wealth where their heart is — in their homes. Nearly a third of the wealth held by the super-rich (those with over $30 million of assets) in Europe is locked in real estate assets worth $2,391 billion, according to data from Savills, a global property consultant. The Asians are second, with $1,800 billion, or nearly 27 per cent of their wealth, in property. Over-investment The super-rich in India, as expected, beat the global averages by a big margin. Nearly 44 per cent […]




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Why Indians do not like to reverse mortgage property

A reverse mortgage is a special type of loan against a home that allows the borrower to convert a portion of the equity in the property into cash. The equity built up over many years of home loan payments can be paid directly to the borrower. However, unlike a traditional home equity loan no repayment is required until the borrower(s) cease to use the home as their principal residence. With a traditional second mortgage, or a home equity line of credit, one must show sufficient income versus debt ratio to qualify for such a loan, and needs to make monthly payments towards the mortgage. Reverse mortgage differs in that it […]



  • Banking and Finance
  • Real Estate India

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Reserve Bank Scheme to Allow Ownership of Property Abroad

KOCHI: You have got some disposable amount, and want to own a real estate asset abroad. Now, it is possible as the Reserve Bank of India (RBI) allows resident Indians to remit money abroad for the purchase of immovable properties. According to a new RBI directive, banks are allowed to remit up to US$125,000 (around Rs 75 lakh) every financial year for any permitted current or capital account transaction, or a combination of both. The money can be used for purchasing immovable property outside India. Financial experts point out that the new norms might be helpful for the state as it would be easier for Keralites to spot properties due […]



  • Banking and Finance
  • Real Estate Developers
  • Real Estate India

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HDFC Property Fund raises $250 mn via offshore fund

Bangalore/Mumbai: HDFC Property Fund, the private equity arm of Housing Development Finance Corp. Ltd, has raised $250 million (around `1,500 crore today) through an offshore fund. It hopes to raise another $150 million by the end of the year, said a person directly familiar with the development who did not want to be named. On Friday, HDFC Property Fund informed the BSE that it had raised the capital through its second international fund, saying “the recently closed fund will focus on investing primarily in residential property developments in major cities across India”. The cumulative assets under management now exceed $1 billion, the statement added. The new fund, which started raising […]




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Belts, Roads, and Regions: The Dynamics of Chinese and Japanese Infrastructure Connectivity Initiatives and Europe’s Responses

East Asia is setting the pace for the recent trend in regional and interregional integration, which is associated with multilateral infrastructure connectivity initiatives.




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Reflections on the Development of Regional Financing Arrangements: Experience from Europe

The European experience could be useful to inspire the future evolution of the Chiang Mai Initiative Multilateralization in the ASEAN+3 membership.




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Creation and Evolution of European Economic and Monetary Union: Lessons for Asian Economic Integration

Asian regional integration is progressing under more complex and diversified considerations than European integration.




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Deintegration in the European Union and Lessons for Asia

Brexit reminds us of the limitations of regional integration.




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Belts, Roads, and Regions: The Dynamics of Chinese and Japanese Infrastructure Connectivity Initiatives and Europe’s Responses

East Asia is setting the pace for the recent trend in regional and interregional integration, which is associated with multilateral infrastructure connectivity initiatives.




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Reflections on the Development of Regional Financing Arrangements: Experience from Europe

The European experience could be useful to inspire the future evolution of the Chiang Mai Initiative Multilateralization in the ASEAN+3 membership.




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St Mary’s Road biz owners set to lose property again

HYDERABAD: Forcible land acquisition has returned to haunt property owners on St Mary’s Road in Secunderabad, who are likely to face the bulldozers for the second time in less than eight years. Incidentally, a sweet shop owner had committed suicide after the lost his only means of livelihood in the first round of acquisition. The arterial road from Secunderabad railway station to Clock Tower was expanded in 2005 by acquiring the properties from 70 owners so that it could be widened from 60 feet to 120 feet. This time, the acquisition is because the metro rail corridor II (JBS-Falaknuma) passes through this road. The Greater Hyderabad Municipal Corporation (GHMC) has […]




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Valuation of property rationalised

Bengal has rationalised property valuation by doing away with the discrepancies between the registration authorities and their actual market value. The move comes into effect across Kolkata and suburbs , sources in real estate body Credai said. Earlier, the registered value of a property was anywhere between 10 and 50 per cent higher than the prevailing market rate. The difference between the market rate and the registered value was deemed as income and taxed. “As a result of this discrepancy many people were either holding back their purchases or not registering their properties ,” Harsh Patodia, President, CREDAI-Bengal, said. http://www.thehindubusinessline.com/news/credai-hails-rationalisation-of-property-valuations-in-bengal/article5614557.ece




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Howrah Municipal Corporation announces partial waiver of property and commercial tax

HOWRAH: With an eye on boosting revenue, the Howrah Municipal Corporation announced a partial waiver for property and commercial tax on Tuesday. Under the waiver scheme, no penalty or interest need to be paid. The KMC has already enforced such a scheme and has benefited greatly, said Howrah mayor Rathin Chakraborty. He said the last board, controlled by the Left Front, bungled in tax collection, resulting in tax default of around Rs 200 crore. “The state is supporting us, but we must be self-sufficient. The tax outstanding will be collected without burdening civilians,” the mayor added. http://timesofindia.indiatimes.com/city/kolkata/Howrah-Municipal-Corporation-announces-partial-waiver-of-property-and-commercial-tax/articleshow/31431111.cms




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Paint house blue-and-white in Kolkata and get full property tax waiver

Kolkata is all set to turn into a blue-and-white city during the Mamata government. The Kolkata Municipal Corporation (KMC) announced Monday that if you paint your house’ exterior blue-and-white, you will be fully exempted from paying property tax to the government. The Trinamool Congress-run KMC has come up with a proposal to waive the property tax for 2014-15 if a residential building or house is painted in the party’s favorite color combination — white and sky blue. “We will allow full waiver of property tax for 2014-15 if anybody wishes to paint his/her house or even apartment buildings, of course residential, in white and sky blue – the theme color […]




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400cr property tax in PMC’s kitty

PUNE: Across the city, the rush to pay the annual property tax in advance and avail the discount has swelled the Pune Municipal Corporation coffers. Over 4.50 lakh property owners, who paid the tax before May 31 and availed of the 10% discount, helped the civic body collect Rs 400 crore in two months. “More than 50% of property owners paid the tax in the first two months of the new financial year. The good response to the scheme is due to the awareness programmes the administration undertook. The efforts to provide bills at the doorstep of residents helped boost collection. A maximum number of bills were sent to the […]



  • Pune
  • Real Estate India

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Indian Property Market Takes A Small Step Out of the Shadows

Few that have bought or even rented real estate in India would be surprised by a recent survey showing the property market here can be maddeningly murky. Jones Lang LaSalle’s Global Real Estate Transparency Index showed that while things have improved, Indian cities still have to work on transparency. The Chicago-based real-estate consultant said India needs to go further to create more clarity on the rules connected to property purchases and real estate prices. “India still scores among the lowest in the transparency of its transaction process,” the report said. Jones Lang LaSalle looked at just over 100 markets around the world and rated them on a dozen parameters ranging […]




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HARMAN Opens First Experience Store in Europe creating a unique space where speed meets sound

MUNICH, Germany – HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, today announced the opening of its first Experience Store in Europe....




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'Never give up': Queen praises Britons on Victory in Europe Day

Britain's Queen Elizabeth honored those who died in World War Two on Friday, the 75th anniversary of Victory in Europe Day, and used the occasion to say she was proud of how people had responded to the coronavirus pandemic.




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Climate change is killing off bumblebees in Europe and North America

Climate change has significantly increased the likelihood of bumblebees being driven to extinction in certain regions across North America and Europe




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Europe’s cave bears may have died out because of their large sinuses

Plant-eating cave bears vanished when ice spread across Europe – maybe because their large sinuses prevented them chewing meat to adapt to the new conditions




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Massive Spinosaurus dinosaur swam through water propelled by its tail

A well-preserved fossilised tail from Spinosaurus suggests this massive dinosaur may have been able to propel itself and hunt for prey in the water




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'Never give up': Queen praises Britons on Victory in Europe Day

Britain's Queen Elizabeth honored those who died in World War Two on Friday, the 75th anniversary of Victory in Europe Day, and used the occasion to say she was proud of how people had responded to the coronavirus pandemic.




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Brexit, 10,000 BC: The untold story of how Britain first left Europe

Megafloods, broken backstops and retreating ice sheets combine in a geological epic: the dramatic story of Britain's protracted original exit from Europe




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'Europe needs a break': EU plots to restart travel and tourism despite COVID

EU states should guarantee vouchers for travel cancelled during the coronavirus pandemic and start lifting internal border restrictions in a bid to salvage some of the summer tourism season, the bloc's executive will say next week.




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The Dream Season 2 review: How the wellness industry ropes people in

The second season of podcast The Dream debunks much of the wellness industry, but creating empathy for the people caught up in it is where the show shines




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Farming and art arose in New Guinea at same time as Europe and Asia

New archaeological finds show that New Guinea developed sophisticated cultural practices around the same time as they were emerging in Europe and Asia




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European coalition takes shape on coronavirus contact-tracing

A European coalition is forming around an approach to using smartphone technology to trace coronavirus infections which, it's hoped, will enable borders to reopen. Joe Davies reports.




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UPDATE 1-"Europe needs a break": EU plots to restart travel and tourism despite COVID

* Tourism, travel, hospitality business hit the hardest by COVID




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European coalition takes shape on coronavirus contact-tracing

A European coalition is forming around an approach to using smartphone technology to trace coronavirus infections which, it's hoped, will enable borders to reopen. Joe Davies reports.




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'Never give up': Queen praises Britons on Victory in Europe Day

Britain's Queen Elizabeth honored those who died in World War Two on Friday, the 75th anniversary of Victory in Europe Day, and used the occasion to say she was proud of how people had responded to the coronavirus pandemic.




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Massive Spinosaurus dinosaur swam through water propelled by its tail

A well-preserved fossilised tail from Spinosaurus suggests this massive dinosaur may have been able to propel itself and hunt for prey in the water




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1 in 4 Toddlers Improperly Vaccinated

Title: 1 in 4 Toddlers Improperly Vaccinated
Category: Health News
Created: 4/30/2008 12:00:00 AM
Last Editorial Review: 4/30/2008 12:00:00 AM




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High Measles Rates Mean Kids, Adults Need Proper Vaccination: CDC

Title: High Measles Rates Mean Kids, Adults Need Proper Vaccination: CDC
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM




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European Society of Cardiology 2020 Congress Goes Virtual

COVID-19 has led the ESC to transition its annual congress to a virtual format; ESC 2020 Congress 'Challenging Times, Infinite Possibilities' will run online from August 29 to September 1.




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UKPMC Rebranded as Europe PMC

With the addition of several European sponsoring agencies, including the European Research Council, UKPMC was renamed Europe PMC as of November 1, 2012. Europe PMC is an outgrowth and expansion of UKPMC, which was first launched in January 2007 with sponsorship from the Wellcome Trust and several other funders of biomedical research in the UK. Europe PMC receives all of its final published articles directly from the U.S. PMC archive. It also accepts and processes author manuscripts of journal articles funded by the Europe PMC sponsoring agencies and makes them available to U.S. PMC and PMC Canada. For more information, see PMC International.




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Minimalistic Cellulosome of the Butanologenic Bacterium Clostridium saccharoperbutylacetonicum

ABSTRACT

Clostridium saccharoperbutylacetonicum is a mesophilic, anaerobic, butanol-producing bacterium, originally isolated from soil. It was recently reported that C. saccharoperbutylacetonicum possesses multiple cellulosomal elements and would potentially form the smallest cellulosome known in nature. Its genome contains only eight dockerin-bearing enzymes, and its unique scaffoldin bears two cohesins (Cohs), three X2 modules, and two carbohydrate-binding modules (CBMs). In this study, all of the cellulosome-related modules were cloned, expressed, and purified. The recombinant cohesins, dockerins, and CBMs were tested for binding activity using enzyme-linked immunosorbent assay (ELISA)-based techniques. All the enzymes were tested for their comparative enzymatic activity on seven different cellulosic and hemicellulosic substrates, thus revealing four cellulases, a xylanase, a mannanase, a xyloglucanase, and a lichenase. All dockerin-containing enzymes interacted similarly with the second cohesin (Coh2) module, whereas Coh1 was more restricted in its interaction pattern. In addition, the polysaccharide-binding properties of the CBMs within the scaffoldin were examined by two complementary assays, affinity electrophoresis and affinity pulldown. The scaffoldin of C. saccharoperbutylacetonicum exhibited high affinity for cellulosic and hemicellulosic substrates, specifically to microcrystalline cellulose and xyloglucan. Evidence that supports substrate-dependent in vivo secretion of cellulosomes is presented. The results of our analyses contribute to a better understanding of simple cellulosome systems by identifying the key players in this minimalistic system and the binding pattern of its cohesin-dockerin interaction. The knowledge gained by our study will assist further exploration of similar minimalistic cellulosomes and will contribute to the significance of specific sets of defined cellulosomal enzymes in the degradation of cellulosic biomass.

IMPORTANCE Cellulosome-producing bacteria are considered among the most important bacteria in both mesophilic and thermophilic environments, owing to their capacity to deconstruct recalcitrant plant-derived polysaccharides (and notably cellulose) into soluble saccharides for subsequent processing. In many ecosystems, the cellulosome-producing bacteria are particularly effective "first responders." The massive amounts of sugars produced are potentially amenable in industrial settings to further fermentation by appropriate microbes to biofuels, notably ethanol and butanol. Among the solvent-producing bacteria, Clostridium saccharoperbutylacetonicum has the smallest cellulosome system known thus far. The importance of investigating the building blocks of such a small, multifunctional nanomachine is crucial to understanding the fundamental activities of this efficient enzymatic complex.




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Burkholderia ubonensis Meropenem Resistance: Insights into Distinct Properties of Class A {beta}-Lactamases in Burkholderia cepacia Complex and Burkholderia pseudomallei Complex Bacteria

ABSTRACT

Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB'-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met.

IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.




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Neuraxial dysraphism in EPAS1-associated syndrome due to improper mesenchymal transition

Objective

To investigate the effect of somatic, postzygotic, gain-of-function mutation of Endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) encoding hypoxia-inducible factor-2α (HIF-2α) on posterior fossa development and spinal dysraphism in EPAS1 gain-of-function syndrome, which consists of multiple paragangliomas, somatostatinoma, and polycythemia.

Methods

Patients referred to our institution for evaluation of new, recurrent, and/or metastatic paragangliomas/pheochromocytoma were confirmed for EPAS1 gain-of-function syndrome by identification of the EPAS1 gain-of-function mutation in resected tumors and/or circulating leukocytes. The posterior fossa, its contents, and the spine were evaluated retrospectively on available MRI and CT images of the head and neck performed for tumor staging and restaging. The transgenic mouse model underwent Microfil vascular perfusion and subsequent intact ex vivo 14T MRI and micro-CT as well as gross dissection, histology, and immunohistochemistry to assess the role of EPAS1 in identified malformations.

Results

All 8 patients with EPAS1 gain-of-function syndrome demonstrated incidental posterior fossa malformations—one Dandy-Walker variant and 7 Chiari malformations without syringomyelia. These findings were not associated with a small posterior fossa; rather, the posterior fossa volume exceeded that of its neural contents. Seven of 8 patients demonstrated spinal dysraphism; 4 of 8 demonstrated abnormal vertebral segmentation. The mouse model similarly demonstrated features of neuraxial dysraphism, including cervical myelomeningocele and spinal dysraphism, and cerebellar tonsil displacement through the foramen magnum. Histology and immunohistochemistry demonstrated incomplete mesenchymal transition in the mutant but not the control mouse.

Conclusions

This study characterized posterior fossa and spinal malformations seen in EPAS1 gain-of-function syndrome and suggests that gain-of-function mutation in HIF-2α results in improper mesenchymal transition.




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Severe Pulmonary Hypertension Management Across Europe (PHAROS): an ERS Clinical Research Collaboration

The past 20 years have seen major advances in the understanding and treatment of pulmonary arterial hypertension (PAH; group 1 of the pulmonary hypertension (PH) clinical classification) [1]. A strong basis of knowledge has been acquired in: 1) large randomised clinical trials for drug development; 2) national registries for epidemiology and outcome; and 3) smaller studies on the pathophysiological mechanisms of the disease. This knowledge has been reviewed at World Symposia on Pulmonary Hypertension (the most recent in 2018 [2]) and summarised in European Respiratory Society (ERS)/European Society of Cardiology (ESC) clinical guidelines (the most recent in 2015 [3, 4]). We are, however, much less knowledgeable on specific aspects such as 1) the implementation of guidelines and access to therapies in different European countries; 2) the management of PH crises and progressive (acute on chronic) heart failure; and 3) other groups of PH, such as PH due to lung diseases. Therapeutic strategies also need to be optimised, in particular regarding the combination of drugs, the use of anticoagulants, the place for new medications targeting different pathophysiological pathways, etc.




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European Respiratory Journal




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Requirement of the Cep57-Cep63 Interaction for Proper Cep152 Recruitment and Centriole Duplication [Research Article]

Cep57 has been characterized as a component of a pericentriolar complex containing Cep63 and Cep152. Interestingly, Cep63 and Cep152 self-assemble into a pericentriolar cylindrical architecture, and this event is critical for the orderly recruitment of Plk4, a key regulator of centriole duplication. However, the way in which Cep57 interacts with the Cep63-Cep152 complex and contributes to the structure and function of Cep63-Cep152 self-assembly remains unknown. We demonstrate that Cep57 interacts with Cep63 through N-terminal motifs and associates with Cep152 via Cep63. Three-dimensional structured illumination microscopy (3D-SIM) analyses suggested that the Cep57-Cep63-Cep152 complex is concentrically arranged around a centriole in a Cep57-in and Cep152-out manner. Cep57 mutant cells defective in Cep63 binding exhibited improper Cep63 and Cep152 localization and impaired Sas6 recruitment for procentriole assembly, proving the significance of the Cep57-Cep63 interaction. Intriguingly, Cep63 fused to a microtubule (MT)-binding domain of Cep57 functioned in concert with Cep152 to assemble around stabilized MTs in vitro. Thus, Cep57 plays a key role in architecting the Cep63-Cep152 assembly around centriolar MTs and promoting centriole biogenesis. This study may offer a platform to investigate how the organization and function of the pericentriolar architecture are altered by disease-associated mutations found in the Cep57-Cep63-Cep152 complex.




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Emergent properties of branching morphologies modulate the sensitivity of coral calcification to high PCO2 [RESEARCH ARTICLE]

Peter J. Edmunds and Scott C. Burgess

Experiments with coral fragments (i.e. nubbins) have shown that net calcification is depressed by elevated PCO2. Evaluating the implications of this finding requires scaling of results from nubbins to colonies, yet the experiments to codify this process have not been carried out. Building from our previous research demonstrating that net calcification of Pocillopora verrucosa (2–13 cm diameter) was unaffected by PCO2 (400 and 1000 µatm) and temperature (26.5 and 29.7°C), we sought generality to this outcome by testing how colony size modulates PCO2 and temperature sensitivity in a branching acroporid. Together, these taxa represent two of the dominant lineages of branching corals on Indo-Pacific coral reefs. Two trials conducted over 2 years tested the hypothesis that the seasonal range in seawater temperature (26.5 and 29.2°C) and a future PCO2 (1062 µatm versus an ambient level of 461 µatm) affect net calcification of an ecologically relevant size range (5–20 cm diameter) of colonies of Acropora hyacinthus. As for P. verrucosa, the effects of temperature and PCO2 on net calcification (mg day–1) of A. verrucosa were not statistically detectable. These results support the generality of a null outcome on net calcification of exposing intact colonies of branching corals to environmental conditions contrasting seasonal variation in temperature and predicted future variation in PCO2. While there is a need to expand beyond an experimental culture relying on coral nubbins as tractable replicates, rigorously responding to this need poses substantial ethical and logistical challenges.




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The effects of elevated temperature and PCO2 on the energetics and haemolymph pH homeostasis of juveniles of the European lobster, Homarus gammarus [RESEARCH ARTICLE]

Daniel P. Small, Piero Calosi, Samuel P. S. Rastrick, Lucy M. Turner, Stephen Widdicombe, and John I. Spicer

Regulation of extracellular acid–base balance, while maintaining energy metabolism, is recognised as an important aspect when defining an organism's sensitivity to environmental changes. This study investigated the haemolymph buffering capacity and energy metabolism (oxygen consumption, haemolymph [l-lactate] and [protein]) in early benthic juveniles (carapace length <40 mm) of the European lobster, Homarus gammarus, exposed to elevated temperature and PCO2. At 13°C, H. gammarus juveniles were able to fully compensate for acid–base disturbances caused by the exposure to elevated seawater PCO2 at levels associated with ocean acidification and carbon dioxide capture and storage (CCS) leakage scenarios, via haemolymph [HCO3] regulation. However, metabolic rate remained constant and food consumption decreased under elevated PCO2, indicating reduced energy availability. Juveniles at 17°C showed no ability to actively compensate haemolymph pH, resulting in decreased haemolymph pH particularly under CCS conditions. Early benthic juvenile lobsters at 17°C were not able to increase energy intake to offset increased energy demand and therefore appear to be unable to respond to acid–base disturbances due to increased PCO2 at elevated temperature. Analysis of haemolymph metabolites suggests that, even under control conditions, juveniles were energetically limited. They exhibited high haemolymph [l-lactate], indicating recourse to anaerobic metabolism. Low haemolymph [protein] was linked to minimal non-bicarbonate buffering and reduced oxygen transport capacity. We discuss these results in the context of potential impacts of ongoing ocean change and CCS leakage scenarios on the development of juvenile H. gammarus and future lobster populations and stocks.




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Microbiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer [Review]

Technologies allowing genetic sequencing of the human microbiome are opening new realms to discovery. The host microbiota substantially impacts immune responses both in immune-mediated inflammatory diseases (IMIDs) and in tumors affecting tissues beyond skin and mucosae. However, a mechanistic link between host microbiota and cancer or IMIDs has not been well established. Here, we propose T helper 17 (TH17) lymphocytes as the connecting factor between host microbiota and rheumatoid or psoriatic arthritides, multiple sclerosis, breast or ovarian cancer, and multiple myeloma. We theorize that similar mechanisms favor the expansion of gut-borne TH17 cells and their deployment at the site of inflammation in extraborder IMIDs and tumors, where TH17 cells are driving forces. Thus, from a pathogenic standpoint, tumors may share mechanistic routes with IMIDs. A review of similarities and divergences in microbiota-TH17 cell interactions in IMIDs and cancer sheds light on previously ignored pathways in either one of the two groups of pathologies and identifies novel therapeutic avenues.




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European Respiratory Review




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Identification of a miR-146b-Fas ligand axis in the development of neutropenia in T large granular lymphocyte leukemia

Tlarge granular lymphocyte leukemia (T-LGLL) is characterized by the expansion of several large granular lymphocyte clones, among which a subset of large granular lymphocytes showing constitutively activated STAT3, a specific CD8+/CD4 phenotype and the presence of neutropenia has been identified. Although STAT3 is an inducer of transcription of a large number of oncogenes, so far its relationship with miRNAs has not been evaluated in T-LGLL patients. Here, we investigated whether STAT3 could carry out its pathogenetic role in T-LGLL through an altered expression of miRNAs. The expression level of 756 mature miRNA was assessed on purified T large granular lymphocytes (T-LGLs) by using a TaqMan Human microRNA Array. Hierarchical Clustering Analysis of miRNA array data shows that the global miRNome clusters with CD8 T-LGLs. Remarkably, CD8 T-LGLs exhibit a selective and STAT3-dependent repression of miR-146b expression, that significantly correlated with the absolute neutrophil counts and inversely correlated with the expression of Fas ligand (FasL), that is regarded as the most relevant factor in the pathogenesis of neutropenia. Experimental evidence demonstrates that the STAT3-dependent reduction of miR-146b expression in CD8 T-LGLs occurs as a consequence of miR-146b promoter hypermethylation and results in the disruption of the HuR-mediated post-transcriptional machinery controlling FasL mRNA stabilization. Restoring miR-146b expression in CD8 T-LGLs lead to a reduction of HuR protein and, in turn, of FasL mRNA expression, thus providing mechanistic insights for the existence of a STAT3-miR146b-FasL axis and neutropenia in T-LGLL.




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Assessing Risks of Polypharmacy Involving Medications With Anticholinergic Properties [Original Research]

PURPOSE

Anticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale.

METHODS

We performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count.

RESULTS

Anticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase).

CONCLUSIONS

The ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials.




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Insight into the structure and tasks of the Early Career Members Committee of the European Respiratory Society

The Early Career Members Committee (ECMC) of the European Respiratory Society (ERS) consists of 14 members, one Early Career Member (ECM) representative per assembly. In September 2019, seven recently elected representatives joined the ECMC. An overview is given of the tasks performed by each representative within the ECMC (table 1). In addition, a short summary about the content of these tasks is provided.




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Continuous professional development: elevating sleep and breathing disorder education in Europe

Sleep and breathing disorders are highly prevalent, representing a growing subspecialty of respiratory medicine. The term sleep disordered breathing (SDB) encompasses a range of conditions characterised by abnormal breathing during sleep, from chronic or habitual snoring, to frank obstructive sleep apnoea (OSA) or, in some cases, central sleep apnoea (CSA) and hypoventilation syndromes. OSA is the commonest form of SDB, leading to many potential consequences and adverse clinical outcomes, including excessive daytime sleepiness, impaired daytime function, metabolic dysfunction, and an increased risk of cardiovascular disease and mortality [1]. The estimated reported prevalence of moderate-to-severe SDB (≥15 events·h–1) was 23.4% in women and 49.7% in men, and the prevalence of symptomatic OSA was 9% and 13%, respectively [2]. However, in some populations, the prevalence of OSA is substantially higher, such as in patients been evaluated for bariatric surgery (estimated range 70–80%), in patients who have had a transient ischaemic attack or stroke (estimated range 60–70%) and in patients with cardiometabolic disease [3–6]. Limited data have been reported on CSA and non-obstructive sleep-related hypoventilation, which have received considerable interest in the sleep field within the past 10 years. Even if their prevalence was noted to be quite low relative to the prevalence of OSA [7], they are quite common in specific subpopulations [8–10].