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Molecular Drivers of Lymphocyte Organization in Vertebrate Mucosal Surfaces: Revisiting the TNF Superfamily Hypothesis [IMMUNOGENETICS]

Key Points

  • Lymphotoxin axis is not essential for formation of O-MALT in ectotherms and birds.

  • Vertebrate O-MALT structures are enriched in neuroactive ligand/receptor genes.

  • Mammalian PPs and LNs are enriched in genes involved in olfactory transduction.




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    Extent of Fermi-surface reconstruction in the high-temperature superconductor HgBa2CuO4+{delta} [Physics]

    High magnetic fields have revealed a surprisingly small Fermi surface in underdoped cuprates, possibly resulting from Fermi-surface reconstruction due to an order parameter that breaks translational symmetry of the crystal lattice. A crucial issue concerns the doping extent of such a state and its relationship to the principal pseudogap and...




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    Mimicry of a biophysical pathway leads to diverse pollen-like surface patterns [Applied Physical Sciences]

    A ubiquitous structural feature in biological systems is texture in extracellular matrix that gains functions when hardened, for example, cell walls, insect scales, and diatom tests. Here, we develop patterned liquid crystal elastomer (LCE) particles by recapitulating the biophysical patterning mechanism that forms pollen grain surfaces. In pollen grains, a...




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    Body surface temperature responses to food restriction in wild and captive great tits [RESEARCH ARTICLE]

    Lucy A. Winder, Stewart A. White, Andreas Nord, Barbara Helm, and Dominic J. McCafferty

    During winter at temperate and high latitudes, the low ambient temperatures, limited food supplies and short foraging periods mean small passerines show behavioural, morphological and physiological adaptations to reduce the risk of facing energy shortages. Peripheral tissues vasoconstrict in low ambient temperatures to reduce heat loss and cold injury. Peripheral vasoconstriction has been observed with food restriction in captivity but has yet to be explored in free-ranging animals. We experimentally food restricted both wild and captive great tits (Parus major) during winter months and measured surface temperatures of the bill and eye region using thermal imaging, to investigate whether birds show rapid local heterothermic responses, which may reduce their thermoregulatory costs when facing a perceived imminent food shortage. Our results of a continuously filmed wild population showed that bill temperature was immediately reduced in response to food restriction compared with when food was available ad libitum, an apparent autonomic response. Such immediacy implies a ‘pre-emptive’ response before the bird experiences any shortfalls in energy reserves. We also demonstrate temporal variation in vasoconstriction of the bill, with bill temperature gradually rising throughout the food restriction after the initial drop. Eye-region temperature in the wild birds remained at similar levels throughout food restriction compared with unrestricted birds, possibly reflecting the need to maintain steady circulation to the central nervous and visual systems. Our findings provide evidence that birds selectively allow the bill to cool when a predictable food supply is suddenly disrupted, probably as a means of minimising depletion of body reserves for a perceived future shortage in energy.




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    ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface [Membrane Biology]

    Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.




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    An arrestin-1 surface opposite of its interface with photoactivated rhodopsin engages with enolase-1 [Protein Structure and Folding]

    Arrestin-1 is the arrestin family member responsible for inactivation of the G protein–coupled receptor rhodopsin in photoreceptors. Arrestin-1 is also well-known to interact with additional protein partners and to affect other signaling cascades beyond phototransduction. In this study, we investigated one of these alternative arrestin-1 binding partners, the glycolysis enzyme enolase-1, to map the molecular contact sites between these two proteins and investigate how the binding of arrestin-1 affects the catalytic activity of enolase-1. Using fluorescence quench protection of strategically placed fluorophores on the arrestin-1 surface, we observed that arrestin-1 primarily engages enolase-1 along a surface that is opposite of the side of arrestin-1 that binds photoactivated rhodopsin. Using this information, we developed a molecular model of the arrestin-1–enolase-1 complex, which was validated by targeted substitutions of charge-pair interactions. Finally, we identified the likely source of arrestin's modulation of enolase-1 catalysis, showing that selective substitution of two amino acids in arrestin-1 can completely remove its effect on enolase-1 activity while still remaining bound to enolase-1. These findings open up opportunities for examining the functional effects of arrestin-1 on enolase-1 activity in photoreceptors and their surrounding cells.




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    Touching the Surface: Diverse Roles for the Flagellar Membrane in Kinetoplastid Parasites [Review]

    While flagella have been studied extensively as motility organelles, with a focus on internal structures such as the axoneme, more recent research has illuminated the roles of the flagellar surface in a variety of biological processes. Parasitic protists of the order Kinetoplastida, which include trypanosomes and Leishmania species, provide a paradigm for probing the role of flagella in host-microbe interactions and illustrate that this interface between the flagellar surface and the host is of paramount importance. An increasing body of knowledge indicates that the flagellar membrane serves a multitude of functions at this interface: attachment of parasites to tissues within insect vectors, close interactions with intracellular organelles of vertebrate cells, transactions between flagella from different parasites, junctions between the flagella and the parasite cell body, emergence of nanotubes and exosomes from the parasite directed to either host or microbial targets, immune evasion, and sensing of the extracellular milieu. Recent whole-organelle or genome-wide studies have begun to identify protein components of the flagellar surface that must mediate these diverse host-parasite interactions. The increasing corpus of knowledge on kinetoplastid flagella will likely prove illuminating for other flagellated or ciliated pathogens as well.




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    The M Protein of Streptococcus pyogenes Strain AP53 Retains Cell Surface Functional Plasminogen Binding after Inactivation of the Sortase A Gene [Article]

    Streptococcus pyogenes (Lancefield group A Streptococcus [GAS]) is a β-hemolytic human-selective pathogen that is responsible for a large number of morbid and mortal infections in humans. For efficient infection, GAS requires different types of surface proteins that provide various mechanisms for evading human innate immune responses, thus enhancing pathogenicity of the bacteria. Many such virulence-promoting proteins, including the major surface signature M protein, are translocated after biosynthesis through the cytoplasmic membrane and temporarily tethered to this membrane via a type 1 transmembrane domain (TMD) positioned near the COOH terminus. In these proteins, a sorting signal, LPXTG, is positioned immediately upstream of the TMD, which is cleaved by the membrane-associated transpeptidase, sortase A (SrtA), leading to the covalent anchoring of these proteins to newly emerging l-Ala–l-Ala cross-bridges of the growing peptidoglycan cell wall. Herein, we show that inactivation of the srtA gene in a skin-tropic pattern D GAS strain (AP53) results in retention of the M protein in the cell membrane. However, while the isogenic AP53 srtA strain is attenuated in overall pathogenic properties due to effects on the integrity of the cell membrane, our data show that the M protein nonetheless can extend from the cytoplasmic membrane through the cell wall and then to the surface of the bacteria and thereby retain its important properties of productively binding and activating fluid-phase host plasminogen (hPg). The studies presented herein demonstrate an underappreciated additional mechanism of cell surface display of bacterial virulence proteins via their retention in the cell membrane and extension to the GAS surface.

    IMPORTANCE Group A Streptococcus pyogenes (GAS) is a human-specific pathogen that produces many surface factors, including its signature M protein, that contribute to its pathogenicity. M proteins undergo specific membrane localization and anchoring to the cell wall via the transpeptidase sortase A. Herein, we explored the role of sortase A function on M protein localization, architecture, and function, employing, a skin-tropic GAS isolate, AP53, which expresses a human plasminogen (hPg)-binding M (PAM) Protein. We showed that PAM anchored in the cell membrane, due to the targeted inactivation of sortase A, was nonetheless exposed on the cell surface and functionally interacted with host hPg. We demonstrate that M proteins, and possibly other sortase A-processed proteins that are retained in the cell membrane, can still function to initiate pathogenic processes by this underappreciated mechanism.




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    Body Surface Examination Facilitated by Digital Microscopy [Innovations in Primary Care]




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    Microbial Diversity in Deep-Subsurface Hot Brines of Northwest Poland: from Community Structure to Isolate Characteristics [Geomicrobiology]

    Deep-subsurface hot brines in northwest Poland, extracted through boreholes reaching 1.6 and 2.6 km below the ground surface, were microbiologically investigated using culture-independent and culture-dependent methods. The high-throughput sequencing of 16S rRNA gene amplicons showed a very low diversity of bacterial communities, which were dominated by phyla Proteobacteria and Firmicutes. Bacterial genera potentially involved in sulfur oxidation and nitrate reduction (Halothiobacillus and Methylobacterium) prevailed in both waters over the sulfate reducers ("Candidatus Desulforudis" and Desulfotomaculum). Only one archaeal taxon, affiliated with the order Thermoplasmatales, was detected in analyzed samples. Bacterial isolates obtained from these deep hot brines were closely related to Bacillus paralicheniformis based on the 16S rRNA sequence similarity. However, genomic and physiological analyses made for one of the isolates, Bacillus paralicheniformis strain TS6, revealed the existence of more diverse metabolic pathways than those of its moderate-temperature counterpart. These specific traits may be associated with the ecological adaptations to the extreme habitat, which suggest that some lineages of B. paralicheniformis are halothermophilic.

    IMPORTANCE Deep-subsurface aquifers, buried thousands of meters down the Earth’s crust, belong to the most underexplored microbial habitats. Although a few studies revealed the existence of microbial life at the depths, the knowledge about the microbial life in the deep hydrosphere is still scarce due to the limited access to such environments. Studying the subsurface microbiome provides unique information on microbial diversity, community structure, and geomicrobiological processes occurring under extreme conditions of the deep subsurface. Our study shows that low-diversity microbial assemblages in subsurface hot brines were dominated by the bacteria involved in biogeochemical cycles of sulfur and nitrogen. Based on genomic and physiological analyses, we found that the Bacillus paralicheniformis isolate obtained from the brine under study differed from the mesophilic species in the presence of specific adaptations to harsh environmental conditions. We indicate that some lineages of B. paralicheniformis are halothermophilic, which was not previously reported.




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    Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival

    Purpose:

    To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

    Experimental Design:

    Tumor-infiltrating lymphocytes (TIL) were quantified by semiautomated whole-slide analysis in brain metastases from 81 lung adenocarcinomas. Multi-color staining enabled phenotyping of TILs (CD3, CD8, and FOXP3) on a single-cell resolution. Molecular determinants of the extent of TILs in brain metastases were analyzed by transcriptomics in a subset of 63 patients. Findings in lung adenocarcinoma brain metastases were related to published multi-omic primary lung adenocarcinoma The Cancer Genome Atlas data (n = 230) and single-cell RNA-sequencing (scRNA-seq) data (n = 52,698).

    Results:

    TIL numbers within tumor islands was an independent prognostic marker in patients with lung adenocarcinoma brain metastases. Comparative transcriptomics revealed that expression of three surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) was closely associated with TIL numbers. Their expression was not only prognostic in brain metastasis but also in primary lung adenocarcinoma. Correlation with scRNA-seq data revealed that brain metastases with high expression of surfactant genes might originate from tumor cells resembling alveolar type 2 cells. Methylome-based estimation of immune cell fractions in primary lung adenocarcinoma confirmed a positive association between lymphocyte infiltration and surfactant expression. Tumors with a high surfactant expression displayed a transcriptomic profile of an inflammatory microenvironment.

    Conclusions:

    The expression of surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) defines an inflamed subtype of lung adenocarcinoma brain metastases characterized by high abundance of TILs in close vicinity to tumor cells, a prolonged survival, and a tumor microenvironment which might be more accessible to immunotherapeutic approaches.




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    The best picture ever taken of the sun reveals its bizarre surface

    The best picture of the sun is more than five times more detailed than the previous highest-resolution images, revealing weird structures on our star’s surface




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    Pluto formed quickly with a deep ocean covering its entire surface

    Pluto’s ancient oceans may have come about just after the icy world was born, melting from ice in a process that suggests the dwarf planet took just 30,000 years to form




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    An asteroid strike may have popped the surface of Mars

    An unusually round and symmetrical deposit on Mars may be the result of an impact that popped the surface of the planet, causing a volcanic eruption less than 200,000 years ago




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    The Ultimate Optimization Problem: How to Best Use Every Square Meter of the Earth's Surface

    Lucas Joppa, founder of Microsoft's AI for Earth program, is taking an engineering approach to environmental issues




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    How long does coronavirus stay on surfaces and can they infect you?

    The coronavirus has been found to stick to surfaces for days – but you’re more likely to catch it when close to infected people, or possibly through droplets spread via plumbing and ventilation systems




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    Bioluminescent waves dazzle surfers in California: 'Never seen anything like it'

    Crowds are coming to see the light show as beaches begin to reopen after an almost month-long closure due to coronavirus

    Mother nature has provided a radical gift to nighttime beach-goers in southern California, in the form of bioluminescent waves that crash and froth with an otherworldly light.

    Related: California surf shimmers with bioluminescence – in pictures

    Continue reading...





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    Bondi beach reopens to swimmers and surfers as coronavirus lockdown relaxed

    Sydney's famous Bondi Beach reopened to swimmers and surfers today, five weeks after it was shut over the coronavirus pandemic.




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    Mandy Patinkin: Viral clip of Homeland star resurfaces and warms hearts during coronavirus lockdown

    'That is the most exciting thing I've ever had happen!'




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    Ellen Pompeo: Grey's Anatomy star criticised for 'victim shaming' Harvey Weinstein's sexual assault accusers in resurfaced video

    'I truly do wonder what's going on inside of her brain,' one outraged tweeter wrote




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    Kevin Spacey compares his downfall to people struggling in pandemic in newly surfaced video

    Actor said he had to ask himself 'who am I?' after his 'world completely changed'





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    Engadget Podcast: Microsoft's Surface bonanza!

    It’s a Microsoft heavy week! This week, Devindra and Cherlynn are joined by Alex Cranz, Gizmodo’s Senior Consumer Tech Editor, to chat about the bevy of new Surface devices. In particular, they explore why the Surface Go 2 and Book 3 are a bit disapp...




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    Surface Go 2 review: Microsoft's tiny PC is only a tiny bit better

    Judging the Surface Go 2 comes down to your expectations. Can you live with slow performance to get a well-designed $400 tablet PC (not including a keyboard)? Or are you OK with spending hundreds extra to get a slightly more capable machine that's as...




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    Microsoft will fix Surface Laptop 3 'hairline fractures' for free

    Microsoft will repair Surface Laptop 3 screens for free, particularly those that suddenly cracked for no discernible reason. Surface owners have been posting online about discovering hairline cracks on their new laptops’ display over the past few mon...




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    The Morning After: Surface Go 2 review

    Scary stories about Zoombombing and privacy leaks may have you feeling tense about setting up a video call. But under current circumstances there aren’t a lot of other options available, so columnist Violet Blue has some advice on what you should (an...




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    Microsoft just revamped its cheapest and fanciest Surface devices

    Two new pairs of headphones join the laptops and tablets in today's announcement.




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    Scientists are developing an anti-coronavirus surface coating based on nanomaterials

    The research by Ben-Gurion University (BGU) and the National Institute of Biotechnology in the Negev (NIBN), has received financial support from the Israel Innovation Authority as part of a call for proposals for coping with the coronavirus.




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    Controlling angular dispersions in optical metasurfaces




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    Author Correction: Quantum metasurfaces with atom arrays




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    Cardiovascular response and sequelae after minimally invasive surfactant therapy in growth-restricted preterm infants




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    Blood pressure load per body surface area is higher in women than in men




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    IL-33/ST2/IL-9/IL-9R signaling disrupts ocular surface barrier in allergic inflammation




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    High-purity orbital angular momentum states from a visible metasurface laser




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    The rough ride of subducting fault surfaces




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    Len-Tex's Surface iQ Wallcoverings Earns Cradle to Cradle Certification

    Joining gDiapers, the US Postal Service and more, Surface iQ's commercial wallcoverings have earned Cradle to Cradle certification. The only printed commercial grade wallcovering to have earned this certification, Surface iQ's products have an




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    Tapping the Energy Below the Earth's Surface

    The heat in the upper six miles of the earth's crust contains 50,000 times as much energy as found in all the world's oil and gas reserves combined. Despite this abundance, only 10,700 megawatts of geothermal electricity




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    Energy News: BP Oil Spill Woes Continue, Resurface; Kenya's Geothermal Power Doubles; More

    Plus... Shell announces first carbon capture project in the Alberta Tar Sands; Arctic oil and natural gas's high cost to limit their global share.




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    Boxy building minimizes surface, maximizes air and stairs

    Sweden shows how to build comfortable apartments for families, and stairs that people want to use.




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    Bamboo And Soy Improve Surfing

    "Surfboards of




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    Surf eCo School Saves Rainforest

    Torrey Trust, owner of Surf eCo, wanted to do more to protect the oceans and the environment so she opened up her own surf school that teaches kids young and old about the environment while helping them catch a few waves. Located in Encinitas, CA,




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    Resurf: First Group to Recycle Surfboards and Wetsuits

    So you hit a gnarly wave and end up on shore with your board in two pieces. Bummer dude. But your green side can't bear to just trash that board that's gotten you through some pretty wild rides. You could repair it yourself,




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    Surfboard Swap Next Weekend in San Diego

    Now that the summer surfing season has come to a close, (is there ever really an end to surfing season?), it's time to give your board a little TLC, upgrade any thrashed gear and prepare for the big waves of the




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    Mobile coworking bus lets professionals work, hike, bike & surf (Video)

    This renovated bus is a mobile coworking space that brings location-independent professionals out into the great outdoors, combining work with a hike, a bike trip or a surf ride on the waves.




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    UC San Diego students help produce the world's first algae-based surfboard

    Instead of using a conventional polyurethane core, this sustainable surfboard starts with an algae-based foam blank.




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    So you want to learn how to surf? Here’s where to go

    I went to Costa Rica for surf camp at the world's most sustainable surf school – it was amazing.




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    Stock rally continues beneath the surface on investors' hopes for reopenings and testing

    Stocks were down slightly on Tuesday, but beneath the surface lies the continuation of a powerful rally.




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    Microsoft Surface Laptop 3 review: still sleek, just no longer unique

    USB-C, faster processors and new design options continue to keep Microsoft’s Windows 10 laptop near the top of the pile

    Microsoft’s top-quality laptop is now in its third generation, with new ports, new processors and a slight redesign, with the option to ditch the unique Alcantara for plain old aluminium.

    The £999 and up Surface Laptop 3 is Microsoft’s vision of what a traditional laptop should be. For the most part that’s the same as everyone else, with traditional aluminium body, glass-covered screen and hinge that does not rotate all the way round to the back.

    Screen: 13.5in LCD 2256 x 1504 (201 PPI)

    Processor: quad-core Intel Core i5 or i7 (10th generation)

    RAM: 8 or 16GB

    Storage: 128, 256, 512GB or 1TB

    Graphics: Intel Iris Plus

    Operating system: Windows 10 Home

    Camera: 720P front-facing, Windows Hello

    Connectivity: wifi 6 (ax), Bluetooth 5, USB-A, USB-C, headphones, Surface Connect TPM

    Dimensions: 308.1 x 223.3 x 14.5mm

    Weight: 1,265 or 1,288g

    Due to the angle of the side of the machine it can be difficult to plug the magnetic power cable in without lifting the side up for more leverage.

    The black paint can be scratched revealing the silver aluminium underneath.

    The screen supports 10-point touch and Microsoft’s Surface Pen stylus.

    Pros: great keyboard, good trackpad, Alcantara or aluminium, sleek design, USB-A and USB-C port, great screen, good battery life, Windows Hello, powerful processor.

    Cons: no SD card reader, limited configuration options, no Thunderbolt 3, only one USB-C port.

    Surface Laptop 2 review: Microsoft’s sleeker answer to the MacBook Air

    Microsoft Surface Pro 6 review: a fantastic tablet PC you shouldn’t buy

    Microsoft Surface Go review: tablet that’s better for work than play

    Microsoft Surface Studio 2 review: in a class of its own

    16in MacBook Pro review: bigger battery, new keyboard, new Apple

    Apple MacBook Air review: the new default Mac

    Continue reading...




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    Microsoft Surface Pro X review: not yet ready for prime time

    Long battery life, 4G and beautiful design can’t stop it being held back by a lack of apps for its ARM chip

    The Surface Pro X is a glimpse of an ARM-powered Windows future, combining the best bits of phones and computers, but while that future is closer than ever, it isn’t quite ready yet.

    The new £999 Surface Pro X might look like the rest of Microsoft’s Surface tablets on the outside, but it is fundamentally a different beast on the inside.

    Screen: 13in LCD 2880x1920 (267 PPI)

    Processor: Microsoft SQ1 (ARM)

    RAM: 8 or 16GB

    Storage: 128, 256 and 512GB

    Graphics: Adreno 685

    Operating system: Windows 10 Home

    Camera: 10MP rear, 5MP front-facing, Windows Hello

    Connectivity: Wifi ac, Bluetooth 5, 2x USB-C, Surface Connect, LTE, nano sim, esim

    Dimensions: 287 x 208 x 7.3mm

    Weight: 774g

    The screen is far too dim on resuming from sleep until you hit the brightness button, at which point it returns to normal

    The machine ran cool throughout, barely getting warmer than room temperature even when pushed hard

    There’s no real mis-touch rejection at the edges of the screen, which means you have to be careful where you put your fingers when holding the tablet

    Pros: slim, great 13in screen, 4G, kickstand, nine-hour battery, 2x USB-C, quick charging, Windows Hello, brilliant keyboard (essential additional purchase), smart stylus holder, Windows 10

    Cons: not much ARM-native software, no good photo editors, no SD card reader, no headphone socket, no Thunderbolt 3, keyboard not included

    Microsoft Surface Laptop 3 review: still sleek, just no longer unique

    Microsoft Surface Pro 6 review: a fantastic tablet PC you shouldn’t buy

    Microsoft Surface Go review: tablet that’s better for work than play

    Microsoft Surface Studio 2 review: in a class of its own

    16in MacBook Pro review: bigger battery, new keyboard, new Apple

    Apple MacBook Air review: the new default Mac

    Continue reading...