Recently, the other old hand in this new biochemistry, Craig Venter, asked Church during an interview if everything would still be copacetic—in other words, if mirror drugs and enzymes would really perform the exact same way in the mirror world. While drug companies may be salivating after Church’s short-latency positive answer, there is some intriguing evidence that more subtle symmetry-breaking electron spin effects could be at play. In one such conception, electrons originally in heterogenous spin states are released from an enzyme (like NADH synthase) and are subsequently filtered and polarized as they pass through chiral α-helix structures to the site of amino acid synthesis at the other end. This effectively produces “spin up” electrons that, if you can excuse the jargon, participate in the reductive reaction between α-oxo acid and ammonia with only L-amino acids forming according to the Pauli exclusion principle. In any event, to look in the mirror on the wall and see a biology that does not behave exactly like ours would seem to require some significant new parity breakdown in physics, to say the least.Now, olfaction is probably the space where these deuterium switches and chiral switches most informatively converge to elucidate how receptors might operate. In fact, the authors explicitly highlight the fact that their histamine receptor model may have something to say about olfactory receptors. Importantly, both of these receptor classes belong to the so-called GPCR (G-protein coupled receptor) family that vertebrates use to detect odorants; half of our own 800 GPCRs are provisioned almost exclusively to olfaction.The author’s main comments, here, center on the aromatic groups of molecules, features that are typically associated with delocalized electrons. For example, the imidazole ring of histidine (histamine’s the amino acid precursor) is aromatic at all pH values; four of its pi electrons form two double bonds and two from a nitrogen lone pair. The authors propose that a major fallout of deuteration is that the aromatic moiety shrinks the effective C–D distance relative to its C–H value. Aromatic C–H bonds act as proton donors and form weak hydrogen bonds with water molecules and proton acceptors at the receptor binding site. In other words, that deuterated odorants would be a little different from nondeuterated odorants—something that has actually been appreciated for some time. These comments are pointed straight at recent experiments by Luca Turin, who has advanced the theory of molecular vibration sensing in olfaction in which the nose performs an analysis akin to your favorite benchtop device. Depending on the interpretation, that instrument might be part mass spectrometer, part IR spectrometer, and part scanning tunneling microscope. In particular, they question the conclusion of Luca’s group that flies conditioned with progressively deuterated acetophenone could readily distinguished between the deuterated and nondeuterated varieties.In response, Luca quickly noted a few problems. For one, he fairly observes, ‘then how come the flies transfer learning from one deuterated compound to another, and from C-D stretch to C≡N ? By their lights, there should only be a difference in affinity. Why is there a commonality in smell character?’Perhaps more pointedly, he notes that there are no aromatic CH groups in his deturerated musk experiments, only aliphatic groups—something the authors wisely avoid citing. Furthermore, the authors don’t mention other work that shows very good correlations between vibrational spectra and agonist activity in histamine receptors.In a recent popular article, Luca has made a beginning toward a theory that puts the odor character back into the molecule. While not necessarily drugs, odors can be considered a special class of molecules with a much restricted receptor requirement. Due to inherent limitations in detecting volatiles, olfactory receptors can only expect to see molecules reflecting some trade-off in general stickiness and solubility—a compromise that makes specificity the frequent casualty. Luca proposed that GPCRs and their activators may be thought of as more like electronic components than the mechanical devices of the shape-based receptor paradigm. He suggests that cells could offer them in three styles—vibration (V), tunneling (T), and redox (R):Type V receptors tunnel electrons across a gap that corresponds to an energy jump by binding a molecule that possesses one or more vibrations at the correct energy. Type T have the same circuit topology, but without an energy jump. The receptor is turned on when a molecule binds to it and includes a feature, such as a positive charge, that lowers the barrier to electron tunneling. Finally, type r receptors only have the output half of the circuit where the ligand brings in the electron, and then undergoes an oxidation step when bound. Notably, GPCRs are frequently considered to be a predominantly Eukaryotic innovation. There is certainly evidence for GPCR precursors among the domains and motifs of proteins in lower life forms. However, bacteria generally go for more direct-acting receptors with efficient built-in ion channels as opposed to the laggy and protracted toggling of separate downstream ion channels actuated by messy G-protein cascades. For example, both bacteriorhodopsin and our rhodopsin belong to the ‘seven transmembrane domain’ family of proteins, but while rhodopsin is a GPCR, the ancient light-powered bacterial ion pump is probably not.Why is this the case? If the primary job of sensory neurons is simply to encode incoming information into spikes, then what could be better than speedy ligand gated ion channels? One hint is the observation that if mitochondria generated or otherwise quickly fell out of the advent of eukaryotism, and GPCRs were an integral part of that transition, then the expected intracellular effect from GPCRs might be direct control of the locally resident mitochondria. As possible counterpoint, here, one might point to those rare birds, the infinitesimal fairy flies that inexplicably jettison away much of their own neuronal nuclei and mitochondria and basically run on fumes till they expire. Such creatures might still sense and smell, but how well do they really do it? Explore further Citation: Using the ‘deuterium switch’ to understand how receptors work (2016, June 7) retrieved 18 August 2019 from https://phys.org/news/2016-06-deuterium-receptors.html The authors measured changes in the binding affinities of histamine receptor ligands after they replaced the normal buffer solution with D20 (deuterium oxide). In contrast to other kinds of studies in which the ligands themselves had deuterium permanently bound to carbon atoms, a heavy water solution would deuterate the ligand at exchangeable N-H and O-H protons. This trick directly targets the hydrogen bonds that presumably control ligand-receptor interactions and associated ligand-water interactions.There is no shortage of ways in which an extra neutron perturbs the life of a molecule. A two-fold mass gain decreases bond length and increases bond strength. This ultimately changes a number of physical and chemical properties, including molar volume, polarity, electron donation, Van der Waal’s forces, dipolar moment, and lipophilicity. For example, deuterated caffeine is known to elute faster in the lab on a gas chromatograph mass spectrometer. One might even imagine trying to capture nature’s most elusive superbuzz by drinking it. Depending on which of caffeine’s methyl groups were originally deuterated, the cytochrome 450 enzymes that kick off its transformation in your liver (ultimately to formaldehyde) would likely balk at the enzymatically more resistant C-D bonds. This will delay the formation of some metabolites, creating a relative preponderance of others.To put this so-called ‘deuterium switch’ into the perspective of a larger business model, consider another devilish operation known in the pharmaceutical world as a ‘chiral switch.’ While often performed in much the same spirit as the deuterium shuffle, the creation of mirrorland molecules is arguably an even more significant, qualitative, and less predictable transformation. A recent radical report documents the creation of a ‘reverse’ DNA polymerase, presumably constructed from mirror image ‘D’ (or right-handed) amino acids. This polymerase has the ability to write mirror image DNA that winds to the left (as opposed to threading like a familiar right-handed screw).The beauty of this emerging “looking-glass” world is that the southpaw polymerase has some unexpected talents—for one, it also writes RNA. Furthermore, researchers like George Church are already on their way to building mirror ribosomes that could be fed this mirror-RNA. Therapeutic mirror RNAs and proteins would have an unparalleled diplomatic immunity in the cell, rendering drugs made from them virtually untouchable by straight enzymes, in many respects upgrading the old Windows 32 cellular OS to 64-bits. Recept concepts. Credit: Luca Turin Plausibility of the vibrational theory of smell More information: Mojca Kržan et al. The Quantum Nature of Drug-Receptor Interactions: Deuteration Changes Binding Affinities for Histamine Receptor Ligands, PLOS ONE (2016). DOI: 10.1371/journal.pone.0154002 (Phys.org)—The market value for deuterated drugs has recently been estimated at over a billion dollars. Such drugs are simply molecules in which one or more hydrogen atoms are replaced with deuterium. While these kinds of manipulations are known to work wonders as far as breathing new life into aging patents, the overall therapeutic value of this medical manna can be contentious. A recent paper published in PLoS ONE seeks to explain the ‘quantum nature of drug-receptor interactions’ under deuteration using a combined experimental and computational approach. Although a tall order, a more comprehensive and predictive theory of receptor interactions is sorely needed. Perhaps a theory in which the molecular character of drug effects are written less into the receptor and more into the drug itself. © 2016 Phys.org Journal information: PLoS ONE This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
A team of researchers affiliated with institutions in Argentina, the U.S. and Germany has found that there is a way to improve on the “wisdom of the crowd”—separate the people in a given crowd into smaller groups and let them talk about an issue at hand before an answer is given. In their paper published in the journal Nature Human Behavior, the group describes an experiment they carried out with a large crowd of volunteers, and what they learned from it. Most people have heard of the “wisdom of the crowd,” in which individuals in a crowd are privately asked to give an answer to a question, such as how many jelly beans are in a jar. When averaged together, the answer given by the crowd will generally be better than for any given individual. Now, it appears there may be a way to improve the accuracy of a crowd.Some sociologists have suggested that allowing participants in a crowd to talk to one another before giving “wisdom of the crowd” answers would reduce the accuracy of the final average answer because it would likely lead to a herd mentality. The results of the experiment in this new effort suggest such thinking is wrong.In their experiment, the researchers asked 5180 people at a 2015 TED talk in Buenos Aires to answer several simple questions, such estimating the height of the Eiffel Tower, or the number of goals scored in the 201 FIFA World Cup. Each of the respondents was asked to give an answer privately, and then to join with a group of four other individuals to discuss the question. After one minute on each topic, each of the groups was asked for mutually agreed-upon answers to the same questions.The researchers report that the average answers of the 280 groups of five (not all of those who answered the question individually were willing to join a group) was 49.2 percent more accurate than the average crowd response as a whole. This, the team suggests, indicates that allowing some logical discussion into the equation can improve results. © 2018 Phys.org Journal information: Nature Human Behaviour Is that your final answer? Study suggests method for improving individual decisions Explore further More information: Joaquin Navajas et al. Aggregated knowledge from a small number of debates outperforms the wisdom of large crowds, Nature Human Behaviour (2018). DOI: 10.1038/s41562-017-0273-4AbstractThe aggregation of many independent estimates can outperform the most accurate individual judgement1,2,3. This centenarian finding1,2, popularly known as the ‘wisdom of crowds’3, has been applied to problems ranging from the diagnosis of cancer4 to financial forecasting5. It is widely believed that social influence undermines collective wisdom by reducing the diversity of opinions within the crowd. Here, we show that if a large crowd is structured in small independent groups, deliberation and social influence within groups improve the crowd’s collective accuracy. We asked a live crowd (N = 5,180) to respond to general-knowledge questions (for example, “What is the height of the Eiffel Tower?”). Participants first answered individually, then deliberated and made consensus decisions in groups of five, and finally provided revised individual estimates. We found that averaging consensus decisions was substantially more accurate than aggregating the initial independent opinions. Remarkably, combining as few as four consensus choices outperformed the wisdom of thousands of individuals. Credit: CC0 Public Domain Citation: Crowds within crowd found to outperform ‘wisdom of the crowd’ (2018, January 18) retrieved 18 August 2019 from https://phys.org/news/2018-01-crowds-crowd-outperform-wisdom.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Are you a dog lover? Then here is an evening dedicated to man’s best friend that you must visit.‘A cause 4 The Paws’ is an effort to find loving homes for abandoned pets and other Indian street dogs. The event is in collaboration with Delhi Police Dog Squad and PFA to commemorate World Animal Day. It aims to find homes for abandoned dogs who were pets abandoned by their families. They have found their way to the animal shelters, but are now looking for new loving homes. Also Read – ‘Playing Jojo was emotionally exhausting’The event would feature shows which include Delhi Police Dog Show: A display of obedience, sniffing and tracking by the canine sentinels. The performance will showcase extraordinary talents and immaculatetraining. The squad will consist of about 50 dogs who will display some spectacular drills.Next would be ‘Carnival Of Animals’, a dance performance by Nikolina Nikoleski preaching the importance of animals to mankind. From the smooth moves of a wild cat, the gallop of zebra and horse, to the flight of butterflies, the dancers will create the aura of the jungle. The choreography celebrates the spirit and affection of animals toward humans.The highlight of the event will be a catwalk by abandoned dogs. Pedigrees, mixed breeds/Indian breeds and special dogs would together walk the runway.Be there.DETAILWhen: 13 and 14 OctoberWhere: Amphitheatre, Select Citywalk, Saket Timings: 5 pm onwards
Kolkata: The anti-burglary section of Kolkata Police’s Detective Department solved three major burglarycases within a span of one month. The sleuths not only nabbed the criminals but also recovered around Rs 50 lakh of stolen money.According to a source in the detective department, the first case was registered in the last week of May at Posta police station against a person named Babulal Parekh, who had committed criminal breach of trust and duped his employer. He had fled away Also Read – Heavy rain hits traffic, flightswith Rs 34 lakh.Babulal, who was a resident of Rajasthan, had kept his cell phone switched off, which made it difficult for the sleuths to track his movement. The police used modern technology, tracked his bank accounts and finally managed to arrest him from Indore.A major chunk of the stolen money was also recovered.The second case was registered under Shakespeare Sarani Police station by one Sandeep Agarwal, a resident of Middleton Road.Around Rs 16 lakh was stolen from his house. Also Read – Speeding Jaguar crashes into Merc, 2 B’deshi bystanders killedThe prime suspect was carpenter Murshed Ali, who was working at Agarwal’s residence.Police raided his probable hideouts in Panskura and Barasat but on both the occasions he managed to elude them.The sleuths questioned his friends and relatives and learnt that Murshed was an alcoholic and regularly visited bars. Police identified a handful of bars in the city and laid a trap and ultimately nabbed him. They also recovered much of the stolen cash.The third case was the cracking of a theft case of Rs 9 lakh from an office under Jorasanko Police Station area. Soon, after investigations revealed the involvement of an insider in the job,police started interrogating the employees and matched their call records with their statement.One of the employees, Biswajit Pathak, after prolonged interrogation, finally broke down and confessed his crime. The amount was recovered from him.It may be mentioned that in all these cases the anti burglary team was led by the officer in charge of the squadChitradeep Pande.
Director Kunal Kohli’s acting debut Phir Se is yet to get its release date as the filmmaker is not getting a suitable week for it. The Hum Tum director, who is making his foray into acting opposite TV star Jennifer Winget, said he is looking for a good date. “#PhirSe release date being worked. Next few months packed, looking for a good date, once locked music will follow accordingly,” Kunal posted on Twitter.Phir Se, co-directed by Kunal and debut filmmaker Ajay Bhuyan, is said to be based on a separated couple living in London and they are trying to come to terms with the consequences of their split. The trailer of the film released on April 7, 2015. Phir Se was earlier scheduled to hit theatres in May. The film faced legal trouble when writer Jyoti Kapoor filed a suit against the director for copyright infringement.
BALURGHAT: In a significant move, law enforcers and district administration jointly have imposed restrictions on vehicles in Balurghat town for hassle-free traffic movement duringDurga Puja.It has been decided that no vehicle including motorbikes will be allowed in the town for 12 hours between 4 pm and 4 am starting from October 15 to 19.A high-level meeting was conducted at the conference hall of the district administrative building on Tuesday evening. Also Read – Rain batters Kolkata, cripples normal lifeThe meeting was presided over by district magistrate Deepap Priya P.District police chief Prasun Banerjee, additional district magistrate (general) Krittibas Nayak, additional police chief Debasis Nandi, sub-divisional magistrate Isha Mukherjee, district information and cultural officer Shantanu Chakraborty, Balurghat municipality chairman Rajen Shill and Gangarampur municipality chairman Prasanta Mitra were also present.”It is our target to ensure glitch-free Durga Puja. There will be complete restrictions on vehicles and motorbikes between October 15 and 19 from 4 pm to 4 am. TOTO, however, will run in the town to carry passengers as per rules and regulations provided by the local civic body. Besides, a fare-chart will be provided by the municipality shortly to the TOTO pullers to remove any confusion,” the DM said. Also Read – Speeding Jaguar crashes into Mercedes car in Kolkata, 2 pedestrians killedA joint control-room will be operated by both police and civic body officials.Each puja organiser will get five free entry passes for free movement during restrictions. However, none of them will be allowed to enter in and around 100 meter of the puja pandal.The city people will be provided with two mobile numbers along with Whatsapp facility for any complaint.Notably, the same restrictions had also been imposed on vehicles last year.
Kolkata: Kolkata Police has made elaborate arrangements in Park Street which would be enforced from 11:55 pm on Monday to ensure hassle-free Christmas celebration.Enthusiastic city dwellers have started visiting the area since Sunday night and the footfall has been rising since Monday evening. Despite the huge gathering of people, Kolkata Police has managed traffic in such a way that no major congestion occurred in Park Street before its closure for celebration. Sources informed that Park Street and all of its link roads were blocked from 11:55 pm. All Esplanade bound vehicles were diverted through S N Banerjee Road and Exide Crossing. Also Read – Rain batters Kolkata, cripples normal lifePark Street got more and more crowded throughout the day as the festive frenzy took over people. Another attraction which would add to the joy is a musical fountain installed by CESC at Maidan opposite Victoria Memorial. The 150-channel musical fountain has been refurbished and a new programme of music will enthrall the citizens of Kolkata, which has already acquired a special position as one of the most well-illuminated Indian cities. The fountain becomes functional from 5 pm to 9 pm from Christmas Eve. Governor Keshari Nath Tripathi has conveyed his heartiest greetings to the people of Bengal. He wishes that this joyous occasion provides an opportunity to reaffirm our faith in the country’s cultural heritage, spirit of friendship and fraternity among all sections of society. “May the ideals of peace, amity and sacrifice prevail,” the Governor said.