Alphabet Inc's Google said on Friday it has asked employees to take a day off on May 22, to address work-from-home-related burnout during the coronavirus pandemic.

A non-profit organization brings dogs to the Buffalo/Niagra airport to help relieve the stress of holiday traveling. Diane Hodges reports.

Plants have evolved effective strategies to defend themselves against pathogen invasion. Starting from the plasma membrane with the recognition of microbe-associated molecular patterns (MAMPs) via pattern recognition receptors, internal cellular signaling pathways are induced to ultimately fend off the attack. Phospholipase D (PLD) hydrolyzes membrane phospholipids to produce phosphatidic acid (PA), which has been proposed to play a second messenger role in immunity. The Arabidopsis (Arabidopsis thaliana) PLD family consists of 12 members, and for some of these, a specific function in resistance toward a subset of pathogens has been shown. We demonstrate here that Arabidopsis PLD1, but not its close homologs PLD2 and PLD3, is specifically involved in plant immunity. Genetic inactivation of PLD1 resulted in increased resistance toward the virulent bacterium Pseudomonas syringae pv. tomato DC3000 and the necrotrophic fungus Botrytis cinerea. As pld1 mutant plants responded with elevated levels of reactive oxygen species to MAMP treatment, a negative regulatory function for this PLD isoform is proposed. Importantly, PA levels in pld1 mutants were not affected compared to stressed wild-type plants, suggesting that alterations in PA levels are not likely the cause for the enhanced immunity in the pld1 line. Instead, the plasma-membrane-attached PLD1 protein colocalized and associated with the BAK1-INTERACTING RECEPTOR-LIKE KINASES BIR2 and BIR3, which are known negative regulators of pattern-triggered immunity. Moreover, complex formation of PLD1 and BIR2 was further promoted upon MAMP treatment. Hence, we propose that PLD1 acts as a negative regulator of plant immune responses in complex with immunity-related proteins BIR2 and BIR3.

Phosphatidylcholine and phosphatidylethanolamine are two major phospholipid classes in eukaryotes. Each biosynthesis pathway starts with the phosphorylation of choline (Cho) or ethanolamine (Etn) catalyzed by either choline or ethanolamine kinase (CEK). Arabidopsis contains four CEK isoforms, but their isozyme-specific roles in metabolism and development are poorly described. Here, we showed that these four CEKs have distinct substrate specificities in vitro. While CEK1 and CEK2 showed substrate preference for Cho over Etn, CEK3 and CEK4 had clear substrate specificity for Cho and Etn, respectively. In vivo, CEK1, CEK2, and CEK3 exhibited kinase activity for Cho but not Etn, although the latter two isoforms showed rather minor contributions to total Cho kinase activity in both shoots and roots. The knockout mutants of CEK2 and CEK3 both affected root growth, and these isoforms had nonoverlapping cell-type-specific expression patterns in the root meristematic zone. In-depth phenotype analysis, as well as chemical and genetic complementation, revealed that CEK3, a Cho-specific kinase, is involved in cell elongation during root development. Phylogenetic analysis of CEK orthologs in Brassicaceae species showed evolutionary divergence between Etn kinases and Cho kinases. Collectively, our results demonstrate the distinct roles of the four CEK isoforms in Cho/Etn metabolism and plant development.

Kei Jokura, Junko M. Nishino, Michio Ogasawara, and Atsuo Nishino

Ciliary movement is a fundamental process to support animal life, and the movement pattern may be altered in response to external stimuli under the control of nervous systems. Juvenile and adult ascidians have ciliary arrays around their pharyngeal gill slits (stigmata), and continuous beating is interrupted for seconds by mechanical stimuli on other parts of the body. Although it has been suggested that neural transmission to evoke ciliary arrest is cholinergic, its molecular basis has not yet been elucidated in detail. We herein attempted to clarify the molecular mechanisms underlying this neurociliary transmission in the model ascidian Ciona. Acetylcholinesterase histochemical staining showed strong signals on the laterodistal ciliated cells of stigmata, hereafter referred to as trapezial cells. The direct administration of acetylcholine (ACh) and other agonists of nicotinic ACh receptors (nAChRs) onto ciliated cells reliably evoked ciliary arrest that persisted for seconds in a dose-dependent manner. Only one isoform among all nAChR subunits encoded in the Ciona genome, called nAChR-A7/8-1, a relative of vertebrate α7 nAChRs, was expressed by trapezial cells. Exogenously expressed nAChR-A7/8-1 on Xenopus oocytes responded to ACh and other agonists with consistent pharmacological traits to those observed in vivo. Further efforts to examine signaling downstream of this receptor revealed that an inhibitor of phospholipase C (PLC) hampered ACh-induced ciliary arrest. We herein propose that homomeric α7-related nAChR-A7/8-1 mediates neurociliary transmission in Ciona stigmata to elicit persistent ciliary arrest by recruiting intracellular Ca²⁺ signaling.

VOLUME 295 (2020) PAGES 4079–4092There was an error in the abstract. “The pyridinium cation hampers uptake of OPs into the central nervous system (CNS)” should read as “The pyridinium cation hampers uptake into the central nervous system (CNS).”

The Tabaquito batholith (Frontal Cordillera, western Argentina), is mainly composed of shallowly emplaced granodiorite to minor monzogranite with abundant mafic microgranular enclaves. New sensitive high-resolution ion microprobe U–Pb zircon ages of c. 337 Ma (biotite granodiorite) and c. 284 Ma (mafic dyke) along with previously published geochronological data suggest that a long-lived magmatic system formed through at least two magmatic pulses at c. 337 and c. 322 Ma with later superimposition of Permian magmatism. The Tabaquito granitoids are metaluminous, calc-alkalic and magnesian with I-type affinity. Elevated Th/Nb, Y/Nb and La/Nb ratios along with negative Nb–Ta and positive Pb anomalies are consistent with a continental arc setting. Hf, Nd and Sr isotopic composition of the Tabaquito granitoids suggests that their source could result from mixing of an old felsic crustal component and a juvenile mafic to intermediate component. New geochronological and geochemical data together with published data reveal a continuous arc setting from the Carboniferous to the Permian in Argentina, and important magmatic compositional variations through time and space controlled by episodic fluctuations in the subduction angle of the oceanic plate. Reported and compiled data allow us to infer the continuity of the Carboniferous magmatic arc along the west margin of Gondwana.

Supplementary material: Detailed petrography, analytical methods and data, zircon cathodoluminescence images and supplementary figures are available at https://doi.org/10.6084/m9.figshare.c.4763993

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The α7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with α7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility. To overcome the challenges with orthosteric agonists, we have identified a novel selective α7 positive allosteric modulator (PAM), BNC375. This compound is selective over related receptors and potentiates acetylcholine-evoked α7 currents with only marginal effect on the receptor desensitization kinetics. In addition, BNC375 enhances long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo. Systemic administration of BNC375 reverses scopolamine-induced cognitive deficits in rat novel object recognition and rhesus monkey object retrieval detour (ORD) task over a wide range of exposures, showing no evidence of an inverted U-shaped dose-effect curve. The compound also improves performance in the ORD task in aged African green monkeys. Moreover, ex vivo ¹³C-NMR analysis indicates that BNC375 treatment can enhance neurotransmitter release in rat medial prefrontal cortex. These findings suggest that α7 nAChR PAMs have multiple advantages over orthosteric α7 nAChR agonists for the treatment of cognitive dysfunction associated with CNS diseases.

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.

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of ¹⁸F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.

Alphabet Inc's Google said on Friday it has asked employees to take a day off on May 22, to address work-from-home-related burnout during the coronavirus pandemic.

Temperatures in parts of Britain are likely to soar to 24C over the Easter Bank Holiday weekend, but the sunshine could be interrupted by some April showers.

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Follow our live coronavirus updates HERE Coronavirus: the symptoms

Brits should not book summer holidays because there is no end in sight to the lockdown, the Government has suggested.

Retailer also doubles staff discounts and commits to guaranteeing time off for employees over Christmas period

Greece's tourism minister today told Britons he wants them to holiday in his country this summer as he declared they could be safer there than here.

English schools will reopen after coronavirus lockdown in a "phased manner", the Education Secretary confirmed.

The UK is braced for a wet weekend with sunny spells as temperatures drop ahead of the May Bank Holiday.

Britons will enjoy another mini heatwave as temperatures soar to an unseasonably high 25C just in time for the Bank Holiday weekend.

Brits are set to bask in two days of glorious sunshine over the May Bank Holiday weekend, with temperatures creeping up to 26C.

Mayor Sadiq Khan today made an urgent appeal to Londoners not to relax their "monumental effort" to beat coronavirus as the death toll in the capital's hospitals rose to 5,414.

Brits have been urged to stick to the coronavirus lockdown rules over the Bank Holiday weekend as temperatures are set to soar.

Cabinet Secretary Oliver Dowden admitted on Friday morning that the lockdown is facing a major test from the sunny weekend ahead.

Period dramas, real life spycraft thrills, epic stadium tours and freestyle rap battles all feature.

From accidentally making money due to currency fluctuations, to paying down debt, for some Australians cancelled overseas trips have had surprising windfalls

From June 2018 to June 2019, the Australian Bureau of Statistics says Australians made a record 11.3 million trips overseas – double the number of trips just 10 years ago. In the wake of the Covid-19 pandemic, millions of Australians have been forced to cancel or alter their international travel plans.

This has left many Australians struggling to get refunds from travel providers. Flight Centre was charging $300 in processing fees per person, in some cases leading to fees that cost more than the value of the refund, until the Australian Competition and Consumer Commission stepped in and threatened legal action, causing the company to waive fees for trips cancelled by travel providers. The ACCC also warned travel providers against retroactively changing their cancellation policies after tour companies including Topdeck and Intrepid attempted to retrospectively apply updated refund policies that would force customers to take credit rather than cash for cancelled trips.

Price said her 'phobia of water' made things difficult during the tough course

The best bit? It's completely free

There isn't long to wait until the next Bank Holiday

There isn't long to wait until the next Bank Holiday

Lizzie Edmonds speaks to travel expert Simon Calder about whether we should book summer holidays and how travel will be different

From gift-card rackets to online fraud, consumers are under near-constant assault amid what some analysts are calling the country's first-ever trillion-dollar holiday season.

Resist the urge to sunbath and socialise despite hints from the PM lockdown might be eased soon, Dominic Raab said.

Since the 1970s, the Degenhardts dreamed of retiring to Gerroa. Their dream became a reality — but retirement got tougher this month when they were told their supposedly guaranteed monthly income would not be paid until July due to coronavirus.

Jobless international hospitality workers deemed ineligible for the Federal Government's JobKeeper and JobSeeker programs are "heartbroken" at their treatment and turning to restaurants providing free meals during the coronavirus pandemic.

The major online platforms say rental listings are up 8-10 per cent compared to last year, as thousands of Airbnbs and other short-term rentals are expected to move to the long-term market as coronavirus halts travel.

James and Victoria Sylvester were refused a refund when their $10,000 holiday to Dubai was cancelled because of coronavirus. Now hundreds of consumers in similar situations are considering launching a class action.

An Adelaide mother is jailed for stealing from the Catholic Church to pay for expensive overseas holidays and indulgent consumer goods, while a former accountant is also sentenced for stealing from his clients.

The international organization has been forced to cancel in-person meetings due to restrictions on group gatherings.

Closing out another year at BiotechDueDIligence, thank you for following along! Enjoy another round-up of scientific and medical journal articles driving the conversation and newsflow in biotech.There's lots of great #immunology in @sciencemagazine this week! @JSRustenhoven & @jonykipnis (@kipnislab @UVA) author a fascinating Perspective on how immune cells bypass the blood–brain barrier!https://t.co/6QjcNxU0p6 pic.twitter.com/njjnrn9Yej— Seth Thomas Scanlon (@ImmunoEditor) December 20, [...]

The Justice Department today announced that it has reached a settlement agreement with Catholic Healthcare West (CHW) to resolve allegations that CHW engaged in a pattern or practice of citizenship status discrimination by imposing unnecessary and discriminatory hurdles to employment for work-authorized individuals.

It is a holiday dinner and all hell is about to break out in the dining room. One of your relatives asks what you think about the President Donald Trump impeachment proceedings. There is silence around the table because your family is dreading what is about to happen. Everyone knows Uncle Charley loves Trump while…

Planning your holiday party schedule in New York City can be calendar jujitsu, what with work parties, friends parties, family parties, but there are also a few green themed parties that the sustainably minded New Yorker

Looking for that perfect something for the fashion buff in your life? Some are easy to buy for: They'll take any random piece of clothing--from a vintage fringed dress to a Stella McCartney coat--and make it look fashionable