Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

The assembly of the postsynaptic transmitter sensing machinery at inhibitory nerve cell synapses requires the intimate interplay between cell adhesion proteins, scaffold and adaptor proteins, and γ-aminobutyric acid (GABA) or glycine receptors. We developed an in vitro membrane system to reconstitute this process, to identify the essential protein components, and to define their mechanism of action, with a specific focus on the mechanism by which the cytosolic C terminus of the synaptic cell adhesion protein Neuroligin-2 alters the conformation of the adaptor protein Collybistin-2 and thereby controls Collybistin-2-interactions with phosphoinositides (PtdInsPs) in the plasma membrane. Supported hybrid membranes doped with different PtdInsPs and 1,2-dioleoyl-sn-glycero-3-{[N-(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl} nickel salt (DGS-NTA(Ni)) to allow for the specific adsorption of the His6-tagged intracellular domain of Neuroligin-2 (His-cytNL2) were prepared on hydrophobically functionalized silicon dioxide substrates via vesicle spreading. Two different collybistin variants, the WT protein (CB2SH3) and a mutant that adopts an intrinsically 'open' and activated conformation (CB2SH3/W24A-E262A), were bound to supported membranes in the absence or presence of His-cytNL2. The corresponding binding data, obtained by reflectometric interference spectroscopy, show that the interaction of the C terminus of Neuroligin-2 with Collybistin-2 induces a conformational change in Collybistin-2 that promotes its interaction with distinct membrane PtdInsPs.

Despite the continued analysis of HDAC inhibitors in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

Tectonic Politics: Global Political Risk in an Age of Transformation Book sysadmin 7 May 2019

Political risk now affects more markets and countries than ever before and that risk will continue to rise. But traditional methods of managing political risk are no longer legitimate or effective.

In Tectonic Politics, Nigel Gould-Davies explores the complex, shifting landscape of political risk and how to navigate it. He analyses trends in each form of political risk: the power to destroy, seize, regulate, and tax.

He shows how each of these forms reflects a deeper transformation of the global political economy that is reordering the relationship between power, wealth, and values. In a world where everything is political, the craft of engagement is as important as the science of production and the art of the deal.

The successful company must integrate that craft—the engager’s way of seeing and doing—into strategy and culture.

Drawing on a career in academia, business, and diplomacy, Gould-Davies provides corporate leaders, scholars, and engaged citizens with a groundbreaking study of the fastest-rising political risk today. ‘As tectonic plates shape the earth,’ he writes, ‘so tectonic politics forges its governance.’

The book is published as part of the Insights series.

Praise for Tectonic Politics

About the author

Nigel Gould-Davies was an associate fellow of the Russia and Eurasia Programme at Chatham House.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

Online Disinformation and Political Discourse: Applying a Human Rights Framework Research paper sysadmin 5 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law.

This paper examines how human rights frameworks should guide digital technology.

Summary

• Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
• Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
• International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
• The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
• The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
• Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
• The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
• The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

Thinking out loud: Is disinformation here to stay? 10 November 2022 — 6:00PM TO 6:45PM Anonymous (not verified) 25 October 2022 Chatham House

This event is postponed.

Have you ever wondered how Chatham House researchers approach the big deals that become research? Do you enjoy meeting other Chatham House members and engaging with questions that open your mind? ‘Thinking Out Loud’ invites a small group of members to a live, unscripted discussion with a Chatham House researcher. This in-person event is a way for researchers and members to think out loud to help shape ideas for future research.

Kate Jones, Associate Fellow, International Law Programme at Chatham House will pose some key questions facing how speech is governed in an online world:

• How has big tech influenced the way we think about speech and its limitations?

• Can disinformation be eliminated or even greatly reduced?

• Where should the responsibilities fall between government and business when it comes to speech regulation?

• What might the information landscape look like in 10 years’ time? Should that affect how we tackle disinformation today?

As with all members events, questions from the audience drive the conversation.

How do you reach people trapped in a reality shaped by propaganda? Exploring the dark psychology of disinformation, author and academic Peter Pomerantsev draws on lessons from a forgotten World War II operation to suggest strategies for cutting through misinformation and rebuilding trust in facts today.

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Marloes J. A. G. Henckens
Aug 12, 2009; 29:10111-10119
BehavioralSystemsCognitive

Rafael G. Almeida
Oct 18, 2017; 37:10023-10034
Viewpoints

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling, or fasciculation, of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo, we examined male and female TRIM46 knock-out mice. Contrary to previous reports, we find that TRIM46 is dispensable for axon specification and AIS formation. TRIM46 knock-out mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. However, we confirm that TRIM46 is required for microtubule fasciculation. We also show TRIM46 enrichment in the first ~100 μm of axon occurs independently of ankyrinG (AnkG) in vivo, although AnkG is required to restrict TRIM46 only to the AIS. Our results highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain.

The Thomson Reuters Foundation, the corporate charity of the world’s biggest news and information providers, is teaming up with the UN Food and Agriculture Organization (FAO) to improve [...]

Rome, 2 December 2014 – The Ministers of Agriculture of the European Union and of other Mediterranean countries welcomed FAO’s transformational changes implemented in the last two years, and underlined [...]

South-South Cooperation is the mutual sharing and exchange of development solutions - knowledge, experiences and good practices, policies, technology and resources - between and among countries in the global [...]

Since the 1990s, rural transformations have helped millions of people exit poverty while remaining in rural areas. This underscores an important fact: revitalising rural economies helps create jobs for rural [...]

How do you prefer to read? On your phone, on your tablet, on your computer, or in print? And maybe the way you do it today is not the same [...]

The importance of Ukraine and the Russian Federation for global agricultural markets and the risks associated with the war in Ukraine. 

Global exchange of information on compliance with national, regional, and international fisheries laws and regulations governing sustainable fishing is now possible with the launch of the Global [...]

See how, together, the European Union and FAO are leveraging innovative approaches that benefit the global community

Over the weekend, RCMP says officers searched for answers in the death of the toddler, knocking door-to-door on Saturday in Ashern and the surrounding communities of Gypsumville as they canvassed for information that may shed light on the timeline surrounding the child's death.

CBC Winnipeg News host Brittany Greenslade speaks with Canadian gynecologist Dr. Jen Gunter, who is part of a Tuesday panel discussion about health misinformation and how to separate fact from fiction. It's part of Together Against Misinformation Week, a nationwide event that runs until Nov. 17.

Anautogenous female mosquitoes, which ingest a blood meal from warm-blooded vertebrates to produce eggs, have become a valuable model organism for investigating signaling pathways and physiological processes that occur during egg development. Different molecular pathways tightly regulate the initiation of egg development and are governed by a balance among different insect hormones. Gravid (mature egg-carrying) females deposit fully developed eggs at the end of each gonotrophic cycle, which is defined as the time interval between the ingestion of a blood meal to oviposition. An intact eggshell protects the oocyte and embryo inside from external factors such as desiccation, physical damage, etc., and the various eggshell proteins are spatially and temporary deposited during oogenesis. Additionally, follicle resorption (oosorption) during blood meal–induced mosquito ovarian follicle development is an adapted physiological process that optimizes reproductive fitness. Mosquito oocytes grow and mature synchronously throughout oogenesis; however, during the later stages of oogenesis, some oocytes may undergo oosorption if sufficient nutrients are unavailable. This introduction highlights how mosquito egg development can be used to investigate follicular resorption and identify proteins involved in eggshell formation in Aedes aegypti mosquitoes.

MatWeb's new export engine pipes data from its 47,000 material information sheetsdirectly into SolidWorks and COSMOSWorks

Enhanced online parts library addresses growing global demand for online design content

A remarkable story which came to a climax on February 23 this year when OM Ireland took possession of the deeds to Lacken House as their new headquarters and ministry centre.

Over an eight-day period, 18 Ride2Transform cyclists travelled 690 kilometers, participating in a personal journey with the Lord and praying for the country of Malawi.

Turning organic waste into bio-fuel and French-fry oil into bio-diesel; all these are innovative ways of building sustainable income for the church in Kaharlyk.

It's an unforgettable experience!” OM Mexico’s missions training impacts one participant’s life, who then returns to the training as a staff member.

A worker becomes friends with twin sisters and sees God transform both lives.

Participate in a chat about how multimedia tools are transforming teaching and learning in core academic subjects.

Using a new method to turn stripped-down plant cells into other types of cells, Penn State biologists explored how structural banding patterns increase the stability of cell walls. They also explored how their assembly goes astray in mutant plant cells, which could inform methods to break down plant cells for biofuels.

Pia desperately wanted to work but was always confronted with her background. OM gives her a sewing machine and, with it, a new beginning.

This week, SA Money Report focuses on the controversy around the appointment of Arrie Rautenbach as Absa CEO.

Two young Bangladeshi women experienced great joy and release from the OM tailoring courses, bringing dignity, honour and financial gain to their communities and families.

Scientists have spotted microplastics, tiny pieces of plastic smaller than 5 millimeters, in some of the most pristine environments on Earth, from the depths of the Mariana Trench to the snow on Mt. Everest to the mountaintop clouds of China and Japan. Microplastics have been detected in human brains, the bellies of sea turtles and the roots of plants. Now, new research led by Penn State scientists reveals that microplastics in the atmosphere could be affecting weather and climate.

OM workers in Central Asia use technology to develop new discipleship and worship tools for local believers.

One OM couple uses Transformation Prayer Ministry to help followers of Jesus in Central Asia find freedom from lies they have believed.

The U.S. Department of the Treasury and the State of Delaware announced Friday a Memorandum of Understanding (MOU) setting forth information sharing procedures between the Office of Foreign Assets Control (OFAC) and the Delaware Department of Justice. This MOU is intended to: Promote the sharing of certain U.S. economic sanctions-related information between OFAC and the […]

Attorney General Kathleen Jennings urges all Delaware residents who believe they were impacted by the data breach announced by T-Mobile in August 2021 to take appropriate steps to protect their information from identity theft. On August 17,  T-Mobile reported a massive data breach compromising the sensitive personal information of millions of current, former, and prospective […]

Delaware is joining a nationwide Anti-Robocall Litigation Task Force of 50 attorneys general to investigate and take legal action against the telecommunications companies responsible for bringing a majority of foreign robocalls into the United States.

Attorney General Jennings today announced a multistate settlement with Experian Data Corp (“EDC”) for failing to warn affected consumers after it learned that an identity thief was posing as a private investigator and retrieving sensitive personal information from Court Ventures Inc., a database that EDC had purchased. In 2012, the U.S. Secret Service notified EDC […]

The Delaware Department of Natural Resources and Environmental Control (DNREC), along with state and federal partners, will hold a virtual meeting at 6 p.m. Wednesday, April 13 regarding ethylene oxide (EtO) – with the meeting’s focus on public health and safety concerns over Croda, Inc.’s EtO production in the New Castle area.

DOVER, DE (August 30, 2022) – The Division of Public Health (DPH) is releasing a 2020 State Unintentional Drug Overdose Reporting System (SUDORS) fact sheet on all drug overdose deaths that occurred in Delaware. This snapshot contains fatality data abstracted from the state’s Overdose Data to Action (OD2A) collaborative. DPH collects and analyzes unintentional drug overdose […]

DOVER, DE (September 16, 2022) – The Delaware Division of Public Health (DPH) is pleased to share declines in hospitalizations, test positivity rates and the 7-day average of new positive COVID-19 cases continued for the second month in a row.  Deaths also remain low. However, COVID-19 is still circulating in the community, and at higher levels […]

What's the difference between LENGTH and FORMAT in a SAS data set? This article shares the answer, with examples.

The post Lengths and formats in SAS: the long and short of it appeared first on The SAS Dummy.

Offshore wind developer US Wind, Inc. has submitted multiple permit applications to the Delaware Department of Natural Resources and Environmental Control for its wind energy project offshore of Maryland. To inform the public and engage Delawareans in the regulatory process, DNREC will host a public information session on Wednesday, June 5, from 4 to 7 p.m. at Beacon Middle School, 19483 John J. Williams Highway, Lewes, Del.