PENGARUH KONSENTRASI PELARUT DAN LAMA EKSTRAKSI PADA PRODUKSI KARAGENAN

The purpose of this study is to obtain carrageenan from red seaweed Kappaphycus alvarezii using the steam method. In this study the treatment of 4% NaOH and 5% KOH was used and the extraction time was 7 hours and 10 hours. The stages of making carrageenan are; drying, soaking, washing, extraction, settling, filtering, drying and grinding. The results of this study showed that the highest yield was in 4% NaOH treatment, 10-hour extraction time was equal to 18.15%. The lowest water content was obtained from 5% KOH treatment, 10 extraction time which was 1.9%. The best pH value is in 4% NaOH treatment, 10 hours extraction time is 7.58. The best results of gel strength were obtained from 5% KOH treatment, 7 hours extraction time which was 78.3 mm/g/sec.Keyword: Carrageenan, Kappaphycus alvarezii, Steam Method, NaOH, KOH.Penelitian ini bertujuan untuk mendapatkan karaginan dari rumput laut merah Kappaphycus alvarezii dengan menggunakan metode uap. Pada penelitian ini digunakan perlakuan konsentrasi NaOH 4% dan KOH 5% dan waktu ekstraksi 7 jam dan 10 jam. Tahapan pembuatan karaginan ini adalah pengeringan, perendaman, pencucian, ekstraksi, pengendapan, penyaringan, pengeringan dan penggilingan. Hasil penelitian ini diperoleh rendemen terbanyak ada pada perlakuan NaOH 4%, waktu ekstraksi 10 jam yaitu sebesar 18,15%. Kadar air yang paling rendah diperoleh dari perlakuan KOH 5%, waktu ekstraksi 10 yaitu sebesar 1,9%. Nilai pH terbaik ada pada perlakuan NaOH 4%, waktu ekstraksi 10 jam yaitu sebesar 7,58. Hasil penelitian kekuatan gel paling terbaik diperoleh dari perlakuan KOH 5%, waktu ekstraksi 7 jam yaitu sebesar 78,3 mm/g/det.Kata kunci: Karaginan, Kappaphycus alvarezii, Metode Uap, NaOH, KOH

Efek Perendaman Terhadap Kandungan Serat Kasar, pH dan Skor Sensori Rumput Laut Kappaphycus alvarezii

One type of seaweed that is widely used in Indonesia is Kappaphycus alvarezii . This type of seawed is also known as Eucheuma cottonii. The purpose of this study was to compare the value of crude fiber content, pH, and sensory score of Kappaphycus alvarezii after being soaked with 2 different types of water (well water and demineralized water). Soaking process is intended for making seaweed -ice by using dried seaweed as raw material. The parameters tested in this study were crude fiber, pH and sensory using Hedonic scale 1-9. The results indicated that Kappaphycus alvarezii soaked with demineralized water had higher crude fiber content (1.37%) compared to seaweed soaked in well water (1.24%). Likewise, the pH level of seaweed products that are soaked with demineralized water have a higher pH value (6.27) than seaweed products that are soaked in well water (6.19). Furthermore, organoleptic test results show that seaweed products that are soaked with water demineralization was more preferable by panelist in terms of appearance, odor, texture and taste.Salah satu jenis rumput laut yang banyak dimanfaatkan di Indonesia adalah rumput laut Kappaphycus alvarezii . Rumput laut ini juga dikenal dengan nama Eucheuma cottonii. Tujuan penelitian ini adalah membandingkan nilai kadar serat kasar, pH, dan skor sensori rumput laut Kappaphycus alvarezii setelah direndam dengan 2 jenis air berbeda (air sumur dan air demineralisasi). Proses perendaman ditujukan untuk pembuatan es rumput laut dengan menggunakan rumput laut kering. Parameter yang diuji pada penelitian ini adalah serat kasar, pH dan uji sensori menggunakan uji Hedonik skala 1 – 9. Hasil analisa menunjukkan bahwa rumput laut Kappaphycus alvarezii yang direndam dengan air demineralisasi memiliki kandungan serat kasar yang lebih tinggi (1.37%) dibandingkan dengan rumput laut yang direndam dengan air sumur (1.24%). Pada pengujian kadar pH, produk rumput laut yang direndam dengan air demineralisasi memiliki nilai pH yang lebih tinggi (6.27) dari pada produk rumput laut yang direndam dengan air sumur (6.19), Selanjutnya, hasil uji organoleptik menunjukkan bahwa produk rumput laut yang direndam dengan air demineralisasi lebih disukai panelis dari segi kenampakan, bau, tekstur dan rasa

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus

Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans

The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD

Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a

Rationale Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. Objectives We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Methods Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Results Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. Conclusions PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss.

The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD