Category: biotech/medical – Page 1,534
NHS England » NHS runs world-first test into ‘sci-fi like’ artificial pancreases
Almost 1,000 adults and children with type 1 diabetes have been given a potentially life-altering ‘artificial pancreas’ by the NHS in England as part of the first nationwide test into the effectiveness of this technology in the world.
Health and high quality care for all, now and for future generations.
Hyper-CEST NMR technique reveals missing structure of a novel container molecule
Using the Hyper-CEST NMR technique, the team led by Leif Schröder from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and the Deutsches Krebsforschungszentrum (DKFZ) has managed to reveal two previously little researched variants of a type of transport container from the class of metal–organic polyhedra (MOPs). The researchers want to use this knowledge to develop a novel type of contrast agent in MR (magnetic resonance) imaging.
The concept of a modular construction system proves useful in many applications for assembling complex structures for specific functions from individual, repeated sub-units. In chemistry, the principle can be used to construct a self-assembling network from smaller molecular units that acts as a transport container of a defined size. For example, several metal ions can be linked with organic molecules. These MOPs (metal–organic polyhedra) are used, for instance, to capture greenhouse gases or to pave the way for more effective chemotherapeutic agents by loading them with certain drugs, which they then release in the tumor. Several aspects of the behavior of these structures have not yet been adequately explored. This is partly because there are not always appropriate techniques available to observe the loading and unloading of these MOPs at the molecular level —often, no differences can be measured between the empty and loaded variants for either the container or its contents.
In cooperation with a team from the University of Oulu in Finland, Leif Schröder’s research group has now investigated MOPs that spontaneously assemble in solution from iron ions and an organic compound to form tetrahedra. In the process, the organic struts can be attached differently to the iron “nodes.” Essentially, this influences the properties of MOPs, such as their capacity to kill tumor cells. In the case of the MOP under study, however, it was previously thought that only one of the three theoretically predicted variants existed. The other two variants were considered too unstable because no analytical methods were able to detect them. Using a new method of magnetic resonance (hyper-CEST NMR), Schröder’s team member Jabadurai Jayapaul has now succeeded in demonstrating that these previously unknown variants do exist.
CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia
GABAergic dysfunctions have been implicated in the pathogenesis of schizophrenia, especially the associated cognitive impairments. The GABA synthetic enzyme glutamate decarboxylase 67-kDa isoform (GAD67) encoded by the GAD1 gene is downregulated in the brains of patients with schizophrenia. Furthermore, a patient with schizophrenia harboring a homozygous mutation of GAD1 has recently been discovered. However, it remains unclear whether loss of function of GAD1 leads to the symptoms observed in schizophrenia, including cognitive impairment. One of the obstacles faced in experimental studies to address this issue is the perinatal lethality of Gad1 knockout (KO) mice, which precluded characterization at the adult stage. In the present study, we successfully generated Gad1 KO rats using CRISPR/Cas9 genome editing technology.
Behavioral Consequences of a Combination of Gad1 Haplodeficiency and Adolescent Exposure to an NMDA Receptor Antagonist in Long-Evans Rats
Glutamate decarboxylase 67-kDa isoform (GAD67), which is encoded by the GAD1 gene, is one of the key enzymes that produce GABA. The reduced expression of GAD67 has been linked to the pathophysiology of schizophrenia. Additionally, the excitatory glutamatergic system plays an important role in the development of this disorder. Animal model studies have revealed that chronic blockade of NMDA-type glutamate receptors can cause GABAergic dysfunction and long-lasting behavioral abnormalities. Based on these findings, we speculated that Gad1 haplodeficiency combined with chronic NMDA receptor blockade would lead to larger behavioral consequences relevant to schizophrenia in a rat model. In this study, we administered an NMDAR antagonist, MK-801 (0.2 mg/kg), to CRISPR/Cas9-generated Gad1+/− rats during adolescence to test this hypothesis. The MK-801 treated Gad1+/− rats showed a shorter duration in each rearing episode in the open field test than the saline-treated Gad1+/+ rats. In contrast, immobility in the forced swim test was increased and fear extinction was impaired in Gad1+/− rats irrespective of MK-801 treatment. Interestingly, the time spent in the center region of the elevated plus-maze was significantly affected only in the saline-treated Gad1+/− rats. Additionally, the MK-801-induced impairment of the social novelty preference was not observed in Gad1+/− rats. These results suggest that the synergistic and additive effects of Gad1 haplodeficiency and NMDA receptor blockade during adolescence on the pathogenesis of schizophrenia may be more limited than expected. Findings from this study also imply that these two factors mainly affect negative or affective symptoms, rather than positive symptoms.
γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the central nervous system (Obata, 2013). Post-mortem brain studies on schizophrenia have shown that GABAergic disturbances are part of the pathophysiology of the disorder (Lewis and Sweet, 2009). In particular, the expression level of the GABA-synthesizing enzyme glutamate decarboxylase 67-kDa isoform (GAD67) is lower in the cerebral cortex of patients with schizophrenia than in that of healthy subjects (Guidotti et al., 2000; Volk et al., 2000; Hashimoto et al., 2003; Hashimoto et al., 2008; Curley et al., 2011). GAD67 is encoded by the GAD1 gene, whose SNPs are also suggested to be risk factors for schizophrenia (Addington et al., 2005). We previously reported that Gad1−/− rats displayed some schizophrenia-relevant behaviors, including working memory, which is important for the functional outcome of schizophrenia (Fujihara et al., 2020a).
‘Dark matter’ of human genome finally decoded, sequencing entirety of human DNA
Scientists have been trying to locate the final pieces of the human genome for nearly 20 years, coming close to decoding it but never fully succeeding. Until now.
Scientists finally finish decoding entire human genome in major breakthrough: “We finally got it done”
Scientists said this full picture of the genome will give humanity a greater understanding of our evolution and biology while also opening the door to medical discoveries in areas like aging, neurodegenerative conditions, cancer and heart disease.
“We’re just broadening our opportunities to understand human disease,” said Karen Miga, an author of one of the six studies published Thursday.
The research caps off decades of work. The first draft of the human genome was announced in a White House ceremony in 2000 by leaders of two competing entities: an international publicly funded project led by an agency of the U.S. National Institutes of Health and a private company, Maryland-based Celera Genomics.
STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition
Type 1 diabetes is caused by insulin deficiency resulting from immune-mediated destruction of pancreatic beta cells. Its cause is multifactorial, with complex genetic factors and a strong influence of certain HLA types that probably indicates T-cell-mediated disease.1 Despite attempts to halt the autoimmune destruction of the pancreatic islet at disease onset with immunotherapeutic approaches, 1 recovery of pancreatic beta-cell function remains a challenge because type 1 diabetes is not reversible, even early in the disease.
Correspondence from The New England Journal of Medicine — STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition.
Researchers’ novel tool to help develop safer pesticides
The majority of commercial chemicals that enter the market in the United States every year have insufficient health and safety data. For pesticides, the U.S. Environmental Protection Agency uses a variety of techniques to fill data gaps in order to evaluate chemical hazard, exposure and risk. Nonetheless, public concern over the potential threat that these chemicals pose has grown in recent years, along with the realization that traditional animal-testing methods are not pragmatic by means of speed, economics or ethics. Now, researchers at the George Washington University have developed a new computational approach to rapidly screen pesticides for safety, performance and how long they will endure in the environment. Moreover, and most importantly, the new approach will aid in the design of next-generation molecules to develop safer pesticides.
“In many ways, our tool mimics computational drug discovery, in which vast libraries of chemical compounds are screened for their efficacy and then tweaked to make them even more potent against specific therapeutic targets,” Jakub Kostal, an assistant professor of chemistry at GW and principal investigator on the project, said. “Similarly, we use our systems-based approach to modify pesticides to make them less toxic and more degradable, while, at the same time, making sure they retain good performance. It’s a powerful tool for both industry and regulatory agencies that can help design new, safer analogs of existing commercial agrochemicals, and so protect human life, the environment and industry’s bottom line.”
Using their model, the team analyzed 700 pesticides from the EPA’s pesticide registry. The model considered a pesticide’s likely persistence or degradation in the environment over time, its safety, and how well it performed at killing, repelling or controlling the target problem.
How to get a Cuban COVID jab in 1,000 easy steps
On Valentine’s Day 2022 in Havana, Cuba, I received the Soberana Plus booster shot, one of the island nation’s five homegrown COVID-19 vaccines. The jab had been a long time coming.
For the past year, I had been fixated on the idea of being injected with a made-in-Cuba coronavirus vaccine. While obviously not offering protection against the imperial machinations of my homeland and Cuba’s chief antagonist, the United States, the Cuban serums were at least being developed in the interest of global public health rather than pharmaceutical profit or “vaccine apartheid”, as World Health Organization (WHO) Director General Tedros Adhanom Ghebreyesus has described it.
The story of how I finally got my made-in-Cuba booster in Havana.