I interviewed four business leaders in late 2019 to get their perspectives on the biggest obstacles and opportunities organizations are facing. Craig Lemasters was the president and CEO of Assurant Solutions. Under his leadership, Assurant Solutions doubled in size to $4B, underwent a digital transformation to expand an offering of risk management solutions in the […]

Wayward Pines Synopsis Wayward Pines is a mystery thriller television series produced by Fox Network and set to premiere in May of 2015. Based on the book Pines written by Blake Crouch and produced by M. Night Shyamalan Wayward Pines follows the story of an FBI agent Ethan Bruke (played by Matt Dillon), who travels […]

In one way or another, social learning has been part of our lives for a long time. We spend a large amount of time at work. During this time, we are bound to learn from our colleagues and get a chance to talk on mutual topics of interest. Moreover, social media has given an outlet […]

The post Social Learning as a Way to Foster Productivity in the Workplace appeared first on Dumb Little Man.

Planning a little solo jaunt across the land? If this is your first time planning your virgin solo adventure, I understand completely how excited and nervous you are. I was once in your shoes.

Before you slap on your backpack and march out that door, here’s a small checklist of things you might want to do to ensure a better trip.

Research, Research, Research

It doesn’t matter if you’re headed into uncharted territory or a bustling metropolis, it only helps if you already know what to expect when you set foot in your destination. A quick google search should give you enough information on things like the local culture, geography, weather and political climate to start with. Oh, and do not forget to check out the local laws, either-written and unwritten. People have in the past gotten into trouble for using the wrong gesture or for looking the wrong person in the eye. Did you also know that shaking your head can be interpreted as ‘yes’ in India?

“Hi, would you like to buy some drugs?

– Nervously shakes head –

“Great! Here’s two kilograms of cocaine!”

Kuh-Myoo-Nick-Ashion

Learn a few words and phrases from the local language and the appropriate situations to use them in. You would be surprised at how much a ‘Yallah’ or a ‘Habibi’ can get people to warm up to you in the Middle East. Also, knowing the language makes ordering food that much easier. Just saying.

Who Ya’ Gonna Call?

It’s very useful to have in hand a bunch of contacts that you can get in touch with if-knock on wood- you should ever find yourself in trouble, eg: Your home country’s Embassy/Consulate(stolen passports are a thing in some countries you know?), local emergency numbers etc. If you have friends or relatives in the country/area, make sure you have their numbers as well. There’s no telling what kind of emergency you might encounter on the road.

Link Up With Other Travellers And Locals!

This is for many people, the single greatest reward of solo travel-meeting new people. There’s so much you discover from engaging with people from different cultures and backgrounds. Yes, I’m being captain obvious here, but it’s a point that just had to be reiterated.  Being alive in the internet age has its perks.

A slew of apps and websites have made it that much easier for travelers to get in touch with people at their destinations. It doesn’t matter if you’re just hanging out with your host from ‘AirBnB’ and ‘Couchsurfing’ or finding fellow travelers to share in your adventure from ‘Penroads’, you’re guaranteed to meet some cool people on your journey. As a matter of fact, Penroads is the best way for you to connect with international travellers coming in from all over the world, so it’s definitely a useful tool to have (It’s a shameless plug. I am so sorry. But it really works!).

Stay Healthy!

Last but never the least, take care of your body. Stay hydrated. It’s no good if your mind yells “Onward!” and your body groans “Hell no!”. Find out if you need to get vaccinated before setting off. Carry some basic medicines and bandages if you can, especially if you’re venturing into the wilderness. On occasion you might have to be careful about where and what you eat as well. Talk to someone who has travelled to India and you just might hear the story about how the delicious chicken Tikka from a street vendor gave them a bad case of ‘Delhi Belly’.

Happy tripping!

Parag Murali is the Marketing & Happiness Manager at penroads.com. He combines his love for travelling and people into a daily passion for bringing travellers together. You can contact him at parag@penroads.com for just about anything, so feel free!

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

Invitation Only Research Event

Event participants

Usama Otman Essed, Libya Center for Strategic & Future Studies
Chair: Tim Eaton, Middle East and North Africa Programme, Chatham House

Invitation Only Research Event

Event participants

Jason Pack, Non-Resident Fellow, Middle East Institute
Tim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham House
Chair: Elham Saudi, Director, Lawyers for Justice Libya

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

Research Event

Event participants

Xenia Wickett, Project Director, US; Acting Dean, Academy for Leadership in International Affairs, Chatham House
Peter Jones, Director for Defence and International Security, Foreign & Commonwealth Office
Dr Jamie Shea, Deputy Assistant Secretary General for Emerging Security Challenges, NATO
Chair: Steven Erlanger, London Bureau Chief, New York Times

21 July 2014

For more than 60 years the North Atlantic Treaty Organization (NATO) has played a critical role in enabling transatlantic security and leading crisis management operations. However, given the current climate of austerity, the imminent end of the Afghanistan operation and recent events in Ukraine, crucial questions are being raised regarding the Alliance’s future priorities.

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research

Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity.

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Invitation Only Research Event

Event participants

Niels Engelschiøn, Director-General, Department for European Affairs, Norwegian Ministry of Foreign Affairs
Chair: Dr Robin Niblett, Director; Chief Executive, Chatham House

Invitation Only Research Event

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews

28 April 2020

The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.

Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity.

Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.

Expert

Expert

With 468 stops served by 26 lines, the New York subway system can make visitors feel lucky when they successfully negotiate one planned trip in a day. Yet these two New Yorkers, Chris Solarz and Matt Ferrisi, took on the task of breaking a world record by visiting every stop in the system in less than 24 hours. They used mathematics, especially graph theory, to narrow down the possible routes to a manageable number and subdivided the problem to find the best routes in smaller groups of stations. Then they paired their mathematical work with practice runs and crucial observations (the next-to-last car stops closest to the stairs) to shatter the world record by more than two hours!

Although Chris and Matt.s success may not have huge ramifications in other fields, their work does have a lot in common with how people do modern mathematics research

* They worked together, frequently using computers and often asking experts for advice;
* They devoted considerable time and effort to meet their goal; and
* They continually refined their algorithm until arriving at a solution that was nearly optimal.
Finally, they also experienced the same feeling that researchers do that despite all the hours and intense preparation, the project .felt more like fun than work.
For More Information: Math whizzes shoot to set record for traversing subway system,. Sergey Kadinsky and Rich Schapiro, New York Daily News, January 22, 2009.
Photo by Elizabeth Ferrisi.
Map New York Metropolitan Transit Authority.
The Mathematical Moments program promotes appreciation and understanding of the role mathematics plays in science, nature, technology, and human culture.

Van Wedeen talks about the geometry of the brain's communication pathways.

Hydel, despite trailing their rivals for two straight days, easily retained their title

Sovereign nations typically measure economic success in terms of GDP (income) but this approach is risky as it fails to track and measure the impact of this on nature. Inclusive wealth, on the other hand captures financial and produced capital, but also the skills in our workforce (human capital), the cohesion in our society (social capital) and the value of our environment (natural capital).

The office space company has filed for an initial public offering, here are five things you need to know about one of the year's hottest IPOs