Lifeboat Foundation

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).

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.

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.

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 robot 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.”

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 transfer rate 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.

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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.

The man was walking along a river when he made the amazing discovery, which experts estimate to be around 84 million years old.

Kelly and photographer Carlton Ward Jr. are featured in the April issue of National Geographic magazine. The article provides a glimpse into the life of the Florida panther, whose population once dwindled to below two dozen but has since rebounded to more than 200. Still, serious risks remain. In the past few weeks alone, two more endangered animals were killed after being struck by vehicles. Those deaths highlight a problem — as well as a success story for the cat the Cherokee once called “Lord of the forest.”

To capture panthers on camera, Kelly and Ward first had to find them. That’s not an easy task on Florida’s sandy soil, which makes them hard to track. You have to find really fresh tracks, Kelly said.

“First things first is identifying the track and knowing if it’s a panther or not. And then the real trick is following it,” he said. “So because they go so far, like in any given night, a panther might walk oh, a couple of miles. Maybe more. To actually follow panther tracks to find the panther itself — it’s way harder than it is for any of those African animals. Way harder.”

The patient was completely blind before the treatment — now he can see and count objects on a table.