Lifeboat Foundation

Some might like.

The research team of Gero, a Singapore-based biotech company in collaboration with Roswell Park Comprehensive Cancer Center in Buffalo NY, has presented a study in Nature Communications on associations between aging and the loss of the ability to recover from stresses.

Recently, scientists have reported the first promising examples of biological age reversal by experimental interventions. Indeed, many biological clock types properly predict more years of life for those who choose healthy lifestyles or quit unhealthy ones, such as smoking. Still unknown is how quickly biological age is changing over time for the same individual, and distinguishing between the transient fluctuations and the genuine bioage change trend.

Continue reading “Associations between aging and the loss of the ability to recover from stress” »

Is this the reason why the general public view the emerging field of regenerative medicine with such scepticism? Has a combined cultural history of being bombarded with empty promises of longevity made us numb to such a prospect? Possibly, although I believe it might go deeper than old fashioned scepticism. After all, our species is hardly a stranger to believing something if we desire for it to be true, regardless of how much evidence is presented to us.

Maybe we are simply experiencing just another example of humans finding dramatic change to our way of life hard to comprehend and accept. After all, practically every major change in our recent history was largely believed to be an impossibility by the general public, right up until the point that it became the norm. Everything from the aeroplane to the internet was seen as science fiction, but yet today they are integral parts of our lives. Now, this is not to say that everything the general public is sceptical of will inevitably turn out to prove them wrong, but lessons from our history do show that when it comes to scientific progress, the public will not believe it until they can see it.

Some would believe that scepticism towards regenerative medicine strikes at something much deeper in our psych, as it threatened to fundamentally change our entire outlook on the world. For our entire lives, we have been taught by our interactions with others exactly how life is supposed to progress. You are supposed to suffer a gradual decay of mental and physical abilities, until eventually you die. That is just how it is, and if that were to ever change then we would all have to change how we think about the world. The concept of a 125 year old with the appearance of a 25 year old seems bizarre to us right now, and to many the idea of ever lasting health just goes against their fundamental beliefs of how the world functions to such an extent that they cannot comprehend anything different. Some would even go far as to defend the ageing process as being an integral part of life, displaying what can only be described as ‘Stockholm syndrome with extra steps’.

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.

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

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.

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).

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.

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

The adhesion and colonization or biofilm formation include primary stage in bacterial infections. Major adhesion virulence factors in this step include type I fimbriae (FimH) and pilli structures for attachment to the host cells^7,8. Furthermore, numerous bacteria secrete toxins and extracellular enzymes which play a crucial role in the apoptosis or necrosis of epithelial cells or immunocytes. Various virulence factors of A. baumannii such as adhesins genes like kpsMII (group 2 capsule synthesis) and fimH, tratT (serum resistance associated), fyuA (yersiniabactin receptor) and iutA (aerobactin receptor) have been investigated previously^9,10. An important polysaccharide for biofilm formation is encoded by pgaABCD locus¹¹. Biofilm production is a strategy to escape from harsh conditions and immune responses, hence play as reservoirs for drug-resistant systemic infections. Biofilm-producing A. baumannii has been isolated from several infectious origins such as pneumonia and devise-associated infections. Bacterial within biofilm can resist significantly more against antibiotics compared to planktonic mode of growth¹². Hence, biofilm-mediated infections are in relapse more frequently¹³.

Therefore, there is an urgent need to enhance the effects of antimicrobials against pathogenic bacteria. In recent years, interest has enhanced towards application of nanoparticles as therapeutic regimens^{14,15,16,17,18,19,20,21}. Silver nanoparticles (AgNPs), which have low toxicity in ecosystems and have high rate of surface capacity, can inhibit accumulation of biofilm materials responsible for evasion and protection^22,23,24.

The aim of this study was to isolate A. baumannii from wound infections, determine their resistance and virulence profile, and assess the impact of AgNPs on the bacterial growth, virulence and biofilm-related gene expressions in the isolated strains.