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Of 25000+ people who tested positive for #COVID19 in Germany, 8% had very high viral loads; about a third of these had little to no symptoms. The results suggest asymptomatic people can be expected to be as infectious as hospitalized patients.

Read more from Science:

Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25381 German SARS-CoV-2 cases, including 6110 from test centres attended by pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects, 9519 who were hospitalised, and 1533 B.1.1.7 lineage infections. The youngest had mean log10 viral load 0.5 (or less) lower than older subjects and an estimated ~78% of the peak cell culture replication probability, due in part to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with mean age 37.6. We estimate 4.3 days from onset of shedding to peak viral load (8.1) and cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.

Respiratory disease transmission is highly context dependent and difficult to quantify or predict at the individual level. This is especially the case when transmission from pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects is frequent, as with SARS-CoV-2 (1–8). Transmission is therefore typically inferred from population-level information and summarized as a single overall average, known as the basic reproductive number, R0. While R0 is an essential and critical parameter for understanding and managing population-level disease dynamics, it is a resultant, downstream characterisation of transmission. With regard to SARS-CoV-2, many finer-grained upstream questions regarding infectiousness remain unresolved or unaddressed. Three categories of uncertainty are 1) differences in infectiousness among individuals or groups such as PAMS subjects, according to age, gender, vaccination status, etc.

Continue reading “Estimating infectiousness throughout SARS-CoV-2 infection course” | >

Researchers have also long been chasing lithium-air batteries that could realize a huge jump in energy density. And beyond lithium, there are other entirely different chemistries in development out there. At some point, one of them should click for one application or another.

Lithium-ion or not, an explosion of grid-scale battery installations is coming as prices continue to fall. The nascent art of lithium-ion battery recycling is also sure to mature and expand, improving the sustainability of these batteries by recovering and resetting their chemical building blocks.

Adopt cold-fusion-like skepticism of any of these future-looking statements as you please, but today’s batteries aren’t those of 20 or even 10 years ago. The same thing is bound to be true in another 10 years—even if that progress doesn’t come in a single, giant leap with global fanfare.

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3D printing, also called additive manufacturing, has become widespread in recent years. By building successive layers of raw material such as metals, plastics, and ceramics, it has the key advantage of being able to produce very complex shapes or geometries that would be nearly impossible to construct through more traditional methods such as carving, grinding, or molding.

The technology offers huge potential in the health care sector. For example, doctors can use it to make products to match a patient’s anatomy: a radiologist could create an exact replica of a patient’s spine to help plan surgery; a dentist could scan a patient’s broken tooth to make a perfectly fitting crown reproduction. But what if we took a step further and apply 3D printing techniques to neuroscience?

Stems cells are essentially the body’s raw materials; they are pluripotent elements from which all other cells with specialized functions are generated. The development of methods to isolate and generate human stem cells, has excited many with the promise of improved human cell function understanding, ultimately utilizing them for regeneration in disease and trauma. However, the traditional two-dimensional growth of derived neurones–using flat petri dishes–presents itself as a major confounding factor as it does not adequately mimic in vivo three-dimensional interactions, nor the myriad developmental cues present in real living organisms.

To address this limitation in current neuronal culturing approaches, the FET funded MESO-BRAIN project, led by Aston University, proposed a highly ambitious interdisciplinary enterprise to construct truly 3D networks that not only displayed in vivo activity patterns of neural cultures but also allowed for precise interaction with these cultures. This allows the activity of individual elements to be readily monitored and controlled through electrical stimulation.

The ability to develop human-induced pluripotent stem cell derived neural networks upon a defined and reproducible 3D scaffold that can emulate brain activity, allows for a comprehensive and detailed investigation of neural network development.

Continue reading “3D printing stem cells to transform neuroscience” | >

Aberrant activation of Wnt/β-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/β-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and β-catenin–mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing β-catenin signaling. Compiled functional genomic screens and network analysis revealed unique epigenetic regulators of β-catenin transcriptional output, including the histone lysine methyltransferase 2A oncoprotein (KMT2A/Mll1). Using an integrative epigenomic and transcriptional profiling approach, we show that KMT2A loss diminishes the binding of β-catenin to consensus DNA motifs and the transcription of β-catenin targets in CRC. These results suggest that KMT2A may be a promising target for CRCs and highlight the broader potential for exploiting epigenetic modulation as a therapeutic strategy for β-catenin–driven malignancies.

Colorectal cancer (CRC) represents one of the major malignancies and a leading cause of cancer-related death worldwide. Aberrant Wnt/β-catenin pathway plays a pivotal role in colon carcinogenesis (1). Cytoplasmic β-catenin is phosphorylated by a protein complex containing adenomatous polyposis coli (APC), AXIN1 or AXIN2, casein kinase 1α (CK1α), and glycogen synthase kinase-3β (GSK3β), leading to β-catenin destruction through ubiquitin-proteasome system. Wnt binding to the LDL receptor related protein 5/6 (LRP5/6)–frizzled receptors results in the disassembly of the β-catenin–destruction complex and consequent accumulation of β-catenin. β-Catenin then enters into the nucleus and binds to T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors to initiate the transcription of β-catenin downstream targets (2).

Nearly all colorectal tumors (CRC) harbor genetic mutations that lead to the hyperactivation of β-catenin signaling. For example, germline or spontaneous mutations in tumor suppressor APC may cause constitutive activation of β-catenin in colon stem cells and the development of colonic polyps, which may eventually evolve into colorectal carcinomas. Hyperactivated β-catenin initiates the expression of various downstream targets through binding to the promoter regions via TCF/LEF transcription factors. Studies using transcriptomic approaches have characterized various β-catenin–responsive targets, such as cMYC, AXIN2, ASCL2, LGR5, and CD44. Collectively, these targets promote proliferation (e.g., cMYC) and maintain a stem cell state (e.g., LGR5 and ASCL2), highlighting the potential value of developing treatments that target β-catenin signaling in cancer. However, β-catenin itself is an intractable drug target (6, 7).

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Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson’s disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM.

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While the world was distracted with the rampant spread of a novel coronavirus, 2020 also witnessed an explosion in another deadly pathogen that could pose a threat to global public health.

H5N8, a subtype of highly pathogenic avian influenza virus (HPAIV), was identified decades ago, but during 2020 a series of emerging and ongoing H5N8 outbreaks in avian populations across dozens of countries have led to the death or slaughter of millions of birds worldwide.

“The affected geographic regions have been expanding continuously, and at least 46 countries have reported highly pathogenic H5N8 AIV outbreaks,” virus researchers Weifeng Shi and George F. Gao write in a new perspective article in Science, warning of the dangers of H5N8 if we don’t closely monitor and contain this worrisome trend.

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Creating robots that can perform acrobatic movements such as flips or spinning jumps can be highly challenging. Typically, in fact, these robots require sophisticated hardware designs, motion planners and control algorithms.

Researchers at Massachusetts Institute of Technology (MIT) and University of Massachusetts Amherst recently designed a new humanoid supported by an actuator-aware kino-dynamic motion planner and a landing controller. This design, presented in a paper pre-published on arXiv, could allow the humanoid robot to perform back flips and other acrobatic movements.

“In this work, we tried to come up with realistic control algorithm to make a real humanoid robot perform acrobatic behavior such as back/front/side-flip, spinning jump, and jump over an obstacle,” Donghyun Kim, one of the researchers who developed the robot’s software and controller, told TechXplore. “To do that, we first experimentally identified the actuator performance and then represent the primary limitations in our motion planner.”

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Seagate has been working toward developing a dual-actuator hard drive, meaning that the drive will contain two sets of independently controlled read/write heads. Now, after several years, the company has released its first functional dual-actuator hard drive, the Mach.2. Currently, only enterprises can purchase and use this product, meaning that at least for now, end users will have to wait their turn.

So far, Seagate has reported the Mach.2’s sequential, sustained transfer rate as up to 524MBps—over double the rate of a fast but generic rust disk, closer to the capacity seen in SATA SSD. In fact, this increased carries over into input/output as well, featuring 304 IOPS read / 384 IOPS write and only 4.16 ms average latency. By contrast, normal hard drives usually run at 100/150 IOPS with about the same average latency.

Of course, all of that extra capacity requires additional power. Even while idle, the Mach.2 runs at 7.2 W, while Seagate’s standard Ironwolf line runs at 5 W while idle. That said, it is a bit easier to measure the power specs of Mach.2 than Ironwolf, as the former’s power use can be determined using several random input/output scenarios, as opposed to Ironwolf, whose power is gauged from its “average operating power,” a metric undefined by the Seagate data sheet reference.

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For Ma, growing a more adultlike heart organoid, with all its chambers and structures, is the future of the field. But he doesn’t think this will happen in the next decade. For a complete heartlike organoid, he says, “there is still a long way to go.”

Self-organizing organoids resemble a 1-month-old embryo’s heart.

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