Once upon a time, in a land far, far away – in Internet terms that’s about 10 years ago – a small business owner did not have to worry too much about macro-economics. Well, that was a nice trip down Memory Lane.

Today, Main Street business owners have to operate every day in their micro-economy, while keeping an eye on what is happening at the macro level. Alas, macro-economics is not easy to get your head around when your highest priority on Monday morning is to cover payroll on Friday.

complete article

I'm finally experimenting with writing macros in clojure. Learning macros is (for me at least) a 4 stage process:

1. Learn to use them (pretty straightforward)
2. Learn to read their implementations (including the quoting)
3. Learning to write them (in progress)
4. Learning when to write them (in progress)

Those last two are iterative; #4 is especially tricky -- the web is full of general considerations ("when a function won't do", "when you want new syntax", "when you need to make decisions at compile time", etc) - but actually making that judgment in practice, takes... well practice.

Hence this exercise. Anyway to the code:

Clojure offers the if-let and when-let macros that allow you to combine a let block with testing the binding for nil:

(when-let [a (some-fn)]  
   (do-something-with a))

(if-let [a (some-fn)]  
   (do-something-with a)  
   (otherwise-fn)) 

I found myself (on some real code) wanting to be able to do something similar with try:

(try-let [a (some-potentially-exceptional-fn)]
  (do-something-with a))

(try-let [a (some-potentially-exceptional-fn)]
  (do-something-with a)
  ArithmeticException ((println (.getMessage e)) 42)
  :else (do-something-by-default-fn)
  :finally (println "always"))

etc.

So I wrote this (non-hygenic) macro that seems to do the job:

(defmacro try-let [let-expr good-expr & {fin-expr :finally else-expr :else :as handlers}]
  (letfn [(wrap [arg] (if (seq? arg) arg (list arg)))]
  `(try (let ~let-expr ~good-expr)
    ~@(map #(apply list 'catch (key %) 'e (wrap (val %))) (dissoc handlers :finally :else))
    ~(if else-expr `(catch Exception ~'e ~else-expr))
    (finally ~(if fin-expr `~fin-expr ())))))

Thing is... I don't if it's a good idea or not. For one thing its not hygienic (it implicitly declares e that can be used in the handler clauses) though this seems the kind of case that sort of thing is for.

For another... I don't know if its correct. It seems to be (I've tested all the scenarios I can think of), but this is kinda like security -- I suspect anyone can write a macro that they themselves can't break, but that doesn't mean its correct.

Some things to note: - e is available to handler expressions
- the local function wrap allows for a complex expression or single value to be spliced in
- any number of handlers can be included
- ':else' (default) handler and ':finally' handlers are optional (as are any others!)

In short: I'm interested in any opinions/feedback that aim at learning steps 3 & 4 (writing and when to write). Fire away!

When testing functions, one tests: evaluation result side-effects (if any)

When testing macros, one may also wish to test: expander code expansion

Fr. Anthony talks with Fr. Gregory Jensen about motivated reason and the consequences of mixing micro and macro domains. They suggest that our increasing tribalism is exacerbated of confusing pastoral and public communications - something that is all but impossible to avoid on social media. Enjoy the show!

On semble s'acheminer vers une vague En Marche de forte magnitude aux prochaines Législatives. Si Les Républicains espèrent limiter la casse, c'est à dire avec un perte d'une centaine de députés. L'enjeu de LR, c'est l'après avec en ligne de mire, un...

C’est entendu pour Emmanuel Macron, les violences auraient pour cause les Réseaux Sociaux. Je cite « il y a un changement anthropologique de nos sociétés qui vient des réseaux sociaux ». J’avoue que ce type de raisonnement aussi simplistes me laisse pantois....

1. Notre-Dame de Paris : discours d'Emmanuel Macron, première messe, ouverture au public… Découvrez le calendrier de la réouverture de la cathédrale  franceinfo
2. Réouverture de Notre-Dame : Emmanuel Macron s’exprimera «sur le parvis» de la cathédrale  Le Figaro
3. Réouverture de Notre-Dame de Paris : le calendrier dévoilé, une bonne nouvelle pour les visiteurs  actu.fr
4. Notre-Dame : la cathédrale ouvrira au public du 8 au 14 décembre "jusqu'à 22 heures"  RTL
5. Cérémonies, huit jours de fête, visites: ce qu'il faut savoir sur la réouverture de Notre-Dame de Paris  BFM Paris Ile-de-France

The paper introduces a novel Personal Knowledge Management (PKM) concept and prototype system. The system’s objective is to aid life-long-learning, resourcefulness, creativity, and teamwork of individuals throughout their academic and professional life and as contributors and beneficiaries of organizational and societal performance. Such a scope offers appealing and viable opportunities for stakeholders in the educational, professional, and developmental context. To further validate the underlying PKM application design, the systems thinking techniques of the transdiscipline of Informing Science (IS) are employed. By applying Cohen’s IS-Framework, Leavitt’s Diamond Model, the IS-Meta Approach, and Gill’s and Murphy’s Three Dimensions of Design Task Complexity, the more specific KM models and methodologies central to the PKMS concept are aligned, introduced, and visualized. The extent of this introduction offers an essential overview, which can be deepened and broadened by using the cited URL and DOI links pointing to the available resources of the author’s prior publications. The paper emphasizes the differences of the proposed meme-based PKM System compared to its traditional organizational document-centric counterparts as well as its inherent complementing synergies. As a result, it shows how the system is closing in on Vannevar Bush’s still unfulfilled vison of the ‘Memex’, an as-close-as-it-gets imaginary ancestor celebrating its 70th anniversary as an inspiring idea never realized. It also addresses the scenario recently put forward by Levy which foresees a decentralizing revolution of knowledge management that gives more power and autonomy to individuals and self-organized groups. Accordingly, it also touches on the PKM potential in terms of Kuhn’s Scientific Revolutions and Disruptive Innovations.

Integrating mechanisms into macroecology 

8^th Annual Meeting of the Specialist Group for Macroecology of the Ecological Society of Germany, Austria, and Switzerland (GfÖ)

Martin-Luther-University Halle-Wittenberg, Institute of Biology, Department Geobotany & Botanical Garden, Am Kirchtor 1, 06108 Halle (Saale), Germany

Linking processes and mechanistic approaches (e.g., from physiology, experimental ecology, demography, and evolution) with macroecological approaches, scales, and methods has long been discussed among macroecologists. Still, only few steps toward implementing such links have been taken, yet. With the 8th Annual Meeting of the Specialist Group for Macroecology of the GfÖ, we want to offer a forum for presenting and discussing both tested approaches and new ideas to make these links. Additionally, in order to move beyond discussion, we invite all participants to join the conference workshop on the 2nd day. Here, we plan to intensively discuss gaps in existing approaches and possible ways for bridging these gaps in several discussion groups and to take first steps towards publishing the summarized workshop results. 

http://www.macroecology.org/

The big loser in the French elections was not the far right. It's true that if it hadn't been for the spurious agreements between the New Popular Front and the Macronists, the National Regroupment would have grown even more. But the result of the second round is not exactly a victory for the left. After Marine Le Pen's RN led the first round of the elections, the leaders of the NFP fell into the trap of the French press and Emmanuel Macron, abandoning numerous candidates of their own to increase the chances of the neoliberal right linked to the Renaissance party beating the far right.  The French big bourgeoisie called for a "republican front" to create a "cordon sanitaire" made up of the left and the neoliberal right in order to prevent a landslide victory for the RN, which led to agreements in around 220 constituencies for the candidate with supposedly the least chance of winning the RN to abandon the race in favour of the candidate with the greatest chance. Except that most of the abandonments were by the NFP so that Macron's allies could beat Le Pen's allies, even though the NFP came second in the first round, far ahead of Macron's coalition.

Updated September 16, 2006: In evolutionary biology today macroevolution is used to refer to any evolutionary change at or above the level of species. It means the splitting of a species into two or the change of a species over time into another. This FAQ has been expanded, updated, illustrated, and rewritten.

RAPID (RAtio method Pattern InDexing) is an ImageJ macro script developed for the quick determination of sample orientation and indexing of calibrated and uncalibrated zone axis aligned electron diffraction patterns from materials with a cubic crystal structure. In addition to SAED and NBED patterns, the program is also capable of handling zone axis TEM Kikuchi patterns and FFTs derived from HR(S)TEM images. The software enables users to rapidly determine whether materials are cubic, pseudo-cubic, or non-cubic, and to distinguish between P, I, and F Bravais lattices. It can also provide lattice parameters for material verification and aid in determining the camera constant of the instrument, thus making the program a convenient tool for on-site crystallographic analysis in the TEM laboratory.

N-terminally hexahistidine-tagged O. volvulus macrophage migration inhibitory factor-1 has a unique jellyfish-like structure with the prototypical macrophage migration inhibitory factor trimer as the `head' and a C-terminal extension as the `tail'.

An integrated computer software system for macromolecular crystallography (MX) data collection at the BL02U1 and BL10U2 beamlines of the Shanghai Synchrotron Radiation Facility is described. The system, Finback, implements a set of features designed for the automated MX beamlines, and is marked with a user-friendly web-based graphical user interface (GUI) for interactive data collection. The Finback client GUI can run on modern browsers and has been developed using several modern web technologies including WebSocket, WebGL, WebWorker and WebAssembly. Finback supports multiple concurrent sessions, so on-site and remote users can access the beamline simultaneously. Finback also cooperates with the deployed experimental data and information management system, the relevant experimental parameters and results are automatically deposited to a database.

Structural biology experiments benefit significantly from state-of-the-art synchrotron data collection. One can acquire macromolecular crystallography (MX) diffraction data on large-area photon-counting pixel-array detectors at framing rates exceeding 1000 frames per second, using 200 Gbps network connectivity, or higher when available. In extreme cases this represents a raw data throughput of about 25 GB s−1, which is nearly impossible to deliver at reasonable cost without compression. Our field has used lossless compression for decades to make such data collection manageable. Many MX beamlines are now fitted with DECTRIS Eiger detectors, all of which are delivered with optimized compression algorithms by default, and they perform well with current framing rates and typical diffraction data. However, better lossless compression algorithms have been developed and are now available to the research community. Here one of the latest and most promising lossless compression algorithms is investigated on a variety of diffraction data like those routinely acquired at state-of-the-art MX beamlines.

The extraction and purification procedures, crystallization and crystal structure refinement (single-crystal X-ray data) of germacrone type II, C15H22O, are presented. The structural results are compared with a previous powder X-ray synchrotron study [Kaduk et al. (2022). Powder Diffr. 37, 98–104], revealing significant improvements in terms of accuracy and precision. Hirshfeld atom refinement (HAR), as well as Hirshfeld surface analysis, give insight into the inter­molecular inter­actions of germacrone type II.

The highly cytotoxic macrocyclic trichothecene Isororidin A (C29H40O9) was isolated from the fungus Myrothesium verrucaria endophytic on the wild medicinal plant `Datura' (Datura stramonium L.) and was characterized by one- (1D) and two-dimensional (2D) NMR spectroscopy. The three-dimensional structure of Isororidin A has been confirmed by X-ray crystallography at 0.81 Å resolution from crystals grown in the ortho­rhom­bic space group P212121, with one mol­ecule per asymmetric unit. Isororidin A is the epimer of previously described (by X-ray crystallography) Roridin A at position C-13' of the macrocyclic ring.

This article describes the High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX) at the ESRF, and highlights new and complementary research opportunities that can be explored using this facility. The laboratory is dedicated to investigating interactions between macromolecules and gases in crystallo, and finds applications in many fields of research, including fundamental biology, biochemistry, and environmental and medical science. At present, the HPMX laboratory offers the use of different high-pressure cells adapted for helium, argon, krypton, xenon, nitrogen, oxygen, carbon dioxide and methane. Important scientific applications of high pressure to macromolecules at the HPMX include noble-gas derivatization of crystals to detect and map the internal architecture of proteins (pockets, tunnels and channels) that allows the storage and diffusion of ligands or substrates/products, the investigation of the catalytic mechanisms of gas-employing enzymes (using oxygen, carbon dioxide or methane as substrates) to possibly decipher intermediates, and studies of the conformational fluctuations or structure modifications that are necessary for proteins to function. Additionally, cryo-cooling protein crystals under high pressure (helium or argon at 2000 bar) enables the addition of cryo-protectant to be avoided and noble gases can be employed to produce derivatives for structure resolution. The high-pressure systems are designed to process crystals along a well defined pathway in the phase diagram (pressure–temperature) of the gas to cryo-cool the samples according to the three-step `soak-and-freeze method'. Firstly, crystals are soaked in a pressurized pure gas atmosphere (at 294 K) to introduce the gas and facilitate its inter­actions within the macromolecules. Samples are then flash-cooled (at 100 K) while still under pressure to cryo-trap macromolecule–gas complexation states or pressure-induced protein modifications. Finally, the samples are recovered after depressurization at cryo-temperatures. The final section of this publication presents a selection of different typical high-pressure experiments carried out at the HPMX, showing that this technique has already answered a wide range of scientific questions. It is shown that the use of different gases and pressure conditions can be used to probe various effects, such as mapping the functional internal architectures of enzymes (tunnels in the haloalkane dehalogenase DhaA) and allosteric sites on membrane-protein surfaces, the interaction of non-inert gases with proteins (oxygen in the hydrogenase ReMBH) and pressure-induced structural changes of proteins (tetramer dissociation in urate oxidase). The technique is versatile and the provision of pressure cells and their application at the HPMX is gradually being extended to address new scientific questions.

Over the last decade, the development of time-resolved serial crystallography (TR-SX) at X-ray free-electron lasers (XFELs) and synchrotrons has allowed researchers to study phenomena occurring in proteins on the femtosecond-to-minute timescale, taking advantage of many technical and methodological breakthroughs. Protein crystals of various sizes are presented to the X-ray beam in either a static or a moving medium. Photoactive proteins were naturally the initial systems to be studied in TR-SX experiments using pump–probe schemes, where the pump is a pulse of visible light. Other reaction initiations through small-molecule diffusion are gaining momentum. Here, selected examples of XFEL and synchrotron time-resolved crystallography studies will be used to highlight the specificities of the various instruments and methods with respect to time resolution, and are compared with cryo-trapping studies.

Diffuse scattering is a promising method to gain additional insight into protein dynamics from macromolecular crystallography experiments. Bragg intensities yield the average electron density, while the diffuse scattering can be processed to obtain a three-dimensional reciprocal-space map that is further analyzed to determine correlated motion. To make diffuse scattering techniques more accessible, software for data processing called mdx2 has been created that is both convenient to use and simple to extend and modify. mdx2 is written in Python, and it interfaces with DIALS to implement self-contained data-reduction workflows. Data are stored in NeXus format for software interchange and convenient visualization. mdx2 can be run on the command line or imported as a package, for instance to encapsulate a complete workflow in a Jupyter notebook for reproducible computing and education. Here, mdx2 version 1.0 is described, a new release incorporating state-of-the-art techniques for data reduction. The implementation of a complete multi-crystal scaling and merging workflow is described, and the methods are tested using a high-redundancy data set from cubic insulin. It is shown that redundancy can be leveraged during scaling to correct systematic errors and obtain accurate and reproducible measurements of weak diffuse signals.

Radiation damage remains one of the major impediments to accurate structure solution in macromolecular crystallography. The artefacts of radiation damage can manifest as structural changes that result in incorrect biological interpretations being drawn from a model, they can reduce the resolution to which data can be collected and they can even prevent structure solution entirely. In this article, we discuss how to identify and mitigate against the effects of radiation damage at each stage in the macromolecular crystal structure-solution pipeline.

The formation of a vitrified thin film embedded with randomly oriented macromolecules is an essential prerequisite for cryogenic sample electron microscopy. Most commonly, this is achieved using the plunge-freeze method first described nearly 40 years ago. Although this is a robust method, the behaviour of different macromolecules shows great variation upon freezing and often needs to be optimized to obtain an isotropic, high-resolution reconstruction. For a macromolecule in such a film, the probability of encountering the air–water interface in the time between blotting and freezing and adopting preferred orientations is very high. 3D reconstruction using preferentially oriented particles often leads to anisotropic and uninterpretable maps. Currently, there are no general solutions to this prevalent issue, but several approaches largely focusing on sample preparation with the use of additives and novel grid modifications have been attempted. In this study, the effect of physical and chemical factors on the orientations of macromolecules was investigated through an analysis of selected well studied macromolecules, and important parameters that determine the behaviour of proteins on cryo-EM grids were revealed. These insights highlight the nature of the interactions that cause preferred orientations and can be utilized to systematically address orientation bias for any given macromolecule and to provide a framework to design small-molecule additives to enhance sample stability and behaviour.

Protein crystallography is an established method to study the atomic structures of macromolecules and their complexes. A prerequisite for successful structure determination is diffraction-quality crystals, which may require extensive optimization of both the protein and the conditions, and hence projects can stretch over an extended period, with multiple users being involved. The workflow from crystallization and crystal treatment to deposition and publication is well defined, and therefore an electronic laboratory information management system (LIMS) is well suited to management of the data. Completion of the project requires key information on all the steps being available and this information should also be made available according to the FAIR principles. As crystallized samples are typically shipped between facilities, a key feature to be captured in the LIMS is the exchange of metadata between the crystallization facility of the home laboratory and, for example, synchrotron facilities. On completion, structures are deposited in the Protein Data Bank (PDB) and the LIMS can include the PDB code in its database, completing the chain of custody from crystallization to structure deposition and publication. A LIMS designed for macromolecular crystallography, IceBear, is available as a standalone installation and as a hosted service, and the implementation of key features for the capture of metadata in IceBear is discussed as an example.

Advances in structural biology have relied heavily on synchrotron cryo-crystallography and cryogenic electron microscopy to elucidate biological processes and for drug discovery. However, disparities between cryogenic and room-temperature (RT) crystal structures pose challenges. Here, Cryo2RT, a high-throughput RT data-collection method from cryo-cooled crystals that leverages the cryo-crystallography workflow, is introduced. Tested on endothiapepsin crystals with four soaked fragments, thaumatin and SARS-CoV-2 3CLpro, Cryo2RT reveals unique ligand-binding poses, offers a comparable throughput to cryo-crystallography and eases the exploration of structural dynamics at various temperatures.

AlphaFold2 has revolutionized structural biology by offering unparalleled accuracy in predicting protein structures. Traditional methods for determining protein structures, such as X-ray crystallography and cryo-electron microscopy, are often time-consuming and resource-intensive. AlphaFold2 provides models that are valuable for molecular replacement, aiding in model building and docking into electron density or potential maps. However, despite its capabilities, models from AlphaFold2 do not consistently match the accuracy of experimentally determined structures, need to be validated experimentally and currently miss some crucial information, such as post-translational modifications, ligands and bound ions. In this paper, the advantages are explored of collecting X-ray anomalous data to identify chemical elements, such as metal ions, which are key to understanding certain structures and functions of proteins. This is achieved through methods such as calculating anomalous difference Fourier maps or refining the imaginary component of the anomalous scattering factor f''. Anomalous data can serve as a valuable complement to the information provided by AlphaFold2 models and this is particularly significant in elucidating the roles of metal ions.

The success of experimental phasing in macromolecular crystallography relies primarily on the accurate locations of heavy atoms bound to the target crystal. To improve the process of substructure determination, a modified phase-retrieval algorithm built on the framework of the relaxed alternating averaged reflection (RAAR) algorithm has been developed. Importantly, the proposed algorithm features a combination of the π-half phase perturbation for weak reflections and enforces the direct-method-based tangent formula for strong reflections in reciprocal space. The proposed algorithm is extensively demonstrated on a total of 100 single-wavelength anomalous diffraction (SAD) experimental datasets, comprising both protein and nucleic acid structures of different qualities. Compared with the standard RAAR algorithm, the modified phase-retrieval algorithm exhibits significantly improved effectiveness and accuracy in SAD substructure determination, highlighting the importance of additional constraints for algorithmic performance. Furthermore, the proposed algorithm can be performed without human intervention under most conditions owing to the self-adaptive property of the input parameters, thus making it convenient to be integrated into the structural determination pipeline. In conjunction with the IPCAS software suite, we demonstrated experimentally that automatic de novo structure determination is possible on the basis of our proposed algorithm.

Onchocerca volvulus causes blindness, onchocerciasis, skin infections and devastating neurological diseases such as nodding syndrome. New treatments are needed because the currently used drug, ivermectin, is contraindicated in pregnant women and those co-infected with Loa loa. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) produced, crystallized and determined the apo structure of N-terminally hexahistidine-tagged O. volvulus macrophage migration inhibitory factor-1 (His-OvMIF-1). OvMIF-1 is a possible drug target. His-OvMIF-1 has a unique jellyfish-like structure with a prototypical macrophage migration inhibitory factor (MIF) trimer as the `head' and a unique C-terminal `tail'. Deleting the N-terminal tag reveals an OvMIF-1 structure with a larger cavity than that observed in human MIF that can be targeted for drug repurposing and discovery. Removal of the tag will be necessary to determine the actual biological oligomer of OvMIF-1 because size-exclusion chomatographic analysis of His-OvMIF-1 suggests a monomer, while PISA analysis suggests a hexamer stabilized by the unique C-terminal tails.

With the emergence of ultrafast X-ray sources, interest in following fast processes in small molecules and macromolecules has increased. Most of the current research into ultrafast structural dynamics of macromolecules uses X-ray free-electron lasers. In parallel, small-scale laboratory-based laser-driven ultrafast X-ray sources are emerging. Continuous development of these sources is underway, and as a result many exciting applications are being reported. However, because of their low flux, such sources are not commonly used to study the structural dynamics of macromolecules. This article examines the feasibility of time-resolved powder diffraction of macromolecular microcrystals using a laboratory-scale laser-driven ultrafast X-ray source.

The first Federation of European Biochemical Societies Advanced Course on macromolecular crystallization was launched in the Czech Republic in October 2004. Over the past two decades, the course has developed into a distinguished event, attracting students, early career postdoctoral researchers and lecturers. The course topics include protein purification, characterization and crystallization, covering the latest advances in the field of structural biology. The many hands-on practical exercises enable a close interaction between students and teachers and offer the opportunity for students to crystallize their own proteins. The course has a broad and lasting impact on the scientific community as participants return to their home laboratories and act as nuclei by communicating and implementing their newly acquired knowledge and skills.

VMXm joins the suite of operational macromolecular crystallography beamlines at Diamond Light Source. It has been designed to optimize rotation data collections from protein crystals less than 10 µm and down to below 1 µm in size. The beamline has a fully focused beam of 0.3 × 2.3 µm (vertical × horizontal) with a tuneable energy range (6–28 keV) and high flux (1.6 × 1012 photons s−1 at 12.5 keV). The crystals are housed within a vacuum chamber to minimize background scatter from air. Crystals are plunge-cooled on cryo-electron microscopy grids, allowing much of the liquid surrounding the crystals to be removed. These factors improve the signal-to-noise during data collection and the lifetime of the microcrystals can be prolonged by exploiting photoelectron escape. A novel in vacuo sample environment has been designed which also houses a scanning electron microscope to aid with sample visualization. This combination of features at VMXm allows measurements at the physical limits of X-ray crystallography on biomacromolecules to be explored and exploited.

A new roundtable will hold its first public meeting on Jan. 23 to discuss challenges associated with incorporating climate change into the macroeconomic analyses used for federal policymaking. The roundtable’s activities will inform a new White House interagency working group.

Understanding macroeconomics is helpful as you advance in your OHS career. Macroeconomics is the big picture evaluation of how an economy works based upon numerous influences at the local, regional, and global levels.

MacroEdge Research Highlights National Labor Market Softening with Over 255,000 Job Cuts in Q1, Echoing Sector-Wide Softening Trends

On July 1st, 2023 MacroVerse Games launched Perseverance, the first game in its rules-lite product line.

When it comes to big questions about the economy, we're still kind of in the dark ages. Why do some economies grow so much faster than others? How long is the next recession going to last? How do we stop inflation without wrecking the rest of the economy? These questions are the domain of macroeconomics. But even some macroeconomists themselves admit: While we have many theories about how the economy works, we have very few satisfying answers.

Emi Nakamura wants to change all that. She's a superstar economist who is a pioneer in the field of "empirical macroeconomics." She finds clever ways of using data to untangle some of the oldest mysteries in macroeconomics, about the invisible hand, the consequences of government spending, and the inner workings of inflation.

Recently we called her up to ask her why the economy is so difficult to understand in first place, and how she's trying to find answers anyway. She gets into all of that, and how Jeff Goldblum shaped her career as an economist, in this episode.

This show was hosted by Jeff Guo and Nick Fountain. It was produced by Dave Blanchard with help from Sam Yellowhorse Kesler. It was engineered by Josephine Nyounai and fact checked by Sierra Juarez. Keith Romer edited the show. Alex Goldmark is our executive producer.

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El ejecutivo portugués ha logrado convertir a su grupo en el primer fabricante de vehículos en nuestro país. Y debería aprobar dos nuevos megaproyectos que suman 4.000 millones de euros. Leer

El presidente francés recibe al secretario general de la OTAN en el Elíseo y ambos insisten en la necesidad de seguir apoyando a Ucrania. Leer

Macron: France will 'drive innovation ecosystem of Tech,' president tells Euronews Next

Location: Engineering Library- R857.M3S853 2016

Welcome to an enlightening exploration into the world of macronutrients. These fundamental components of our diet — proteins, carbohydrates, and fats — play integral roles in our body’s physiological functions. While they’re clearly important to our health and well-being, they often remain shrouded in mystery for most of us. By learning more about macronutrients, you’ll understand how ... Read more

The post Macronutrients Unveiled: A Comprehensive Look at Their Roles in a Balanced Diet appeared first on Star Two.

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles

Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.