between

There's a Disconnect Between Parent Expectations and Student Realities

A first look at new federal data on parent involvement suggests a disconnect between parents' expectations and school outcomes.




between

A look at the blurring lines between offline and online retail

Businesses that want to stay competitive are adopting a phygital model to address these demands through the holistic integration of offline and online retail.




between

Google Authenticator Update Allows Transfer of 2FA Codes Between Devices

Google has released an update for its Authenticator app to allow users to manage their account security keys easily while switching to a different phone.




between

Tension Between Stability and Representativeness in a Democratic Setting

Victorien Barbet, Juliette Rouchier, Noé Guiraud and Vincent Laperrière: We present a model showing the evolution of an organization of agents who discuss democratically about good practices. This model feeds on a field study we did for about twelve years in France where we followed NPOs, called AMAP, and observed their construction through time at the regional and national level. Most of the hypothesis we make are here either based on the literature on opinion diffusion or on the results of our field study. By defining dynamics where agents influence each other, make collective decision at the group level, and decide to stay in or leave their respective groups, we analyse the effect of different forms of vertical communication that is meant to spread good practices within the organization. Our main indicators of the good functioning of the democratic dynamics are stability and representativeness. We show that if communication about norms is well designed, it has a positive impact on both stability and representativeness. Interestingly the effect of communication increases with the number of dimensions discussed in the groups. Communication about norms is thus a valuable tool to use in groups that wish to improve their democratic practices without jeopardizing stability.




between

1319 Arbitration of Disputes Between Carriers and Primary Care and Chronic Care Management Providers

DEPARTMENT OF INSURANCE: Office of the Commissioner




between

Your Queries: Mutual Funds -Balanced funds, hybrid funds can switch between equity & debt

Gold ETFs investors can exit only by selling to secondary market participants on the stock exchange.




between

No options: The choice between Trump & Biden is meaningless & proves US democracy is a ‘sham,’ Roger Waters tells RT

With US President Donald Trump preparing to square off with presumptive Democratic nominee Joe Biden in the 2020 race, Americans might as well be choosing between Orwell and Huxley, Pink Floyd co-founder Roger Waters told RT.
Read Full Article at RT.com




between

‘India is an important force’: US Afghanistan envoy Khalilzad calls for direct talks between New Delhi and Taliban

Washington’s special envoy to Afghanistan Zalmay Khalilzad has called on New Delhi to directly engage with the Taliban, asking India to play a “more active” part in the Afghan peace process and the fight against terrorism.
Read Full Article at RT.com




between

UFC 249: An all-time classic between Tony Ferguson and Justin Gaethje beckons as UFC emerges from coronavirus hiatus (VIDEO)

Despite once again being denied seeing Tony Ferguson do battle with Khabib Nurmagomedov, the UFC has served up the next best thing as the fiercely exciting Justin Gaethje steps in to face Ferguson for the interim title at UFC 249.
Read Full Article at RT.com




between

How to setup the peer to peer connection between two Android devices

  Introduction Android* applications may require a peer-to-peer connection between two or more Android* devices without a Wi-Fi access point or Internet access. Two examples of this are file sharing...




between

COVID-19 lockdown: Funny banter between IndiGo, Vistara, AirAsia send Twitterati into a tizzy

After not being able to fly during the nationwide lockdown, Airline companies entertain Twitteratis with an interesting word play on Twitter.




between

An uneasy relationship between telecom & technology

For the next four days, a sprawling conference centre here will become the global hub for the telecommunications and technology industries.




between

Black hole dancing! Scientists study interaction between massive and small black holes

It refers to the difficulty of the direction that takes the small hole around its partner-a difficulty that the research team has now integrated into a highly sophisticated model.




between

Tds under dtaa between uae and india on property sale by nri

AN NRI WANTS TO SELL HIS PROPERTY IN INDIA. UNDER I. TAX PROVISIONS THE BUYER IS SUPPOSED TO DEDUCT TDS @ 20% . WHETHER A LOWER RATE IS THERE UNDER THE data BETWEEN UAE AND INDIA?




between

Tds rate under dtaa between uae and on property sale by nri

IN MY PREVIOUS QUERY THE WORD SHOULD BE DTAA AND NOT DATA.. THANKS.




between

5 Killed In Clash Between Two Groups In Gujarat's Kutch: Police

Five persons were killed in a clash between two groups at Moti Hamirpar village in Kutch district of Gujarat on Saturday afternoon, police said.




between

What's the difference between Cadence PCB Editor and Cadence Allegro?

Are they basically the same thing? I am trying to get as much experience with Allegro since a lot of jobs I am looking at right now are asking for Cadence Allegro experience (I wish they asked for Altium experience...). I currently have access to PCB Editor, but I don't want to commit to learning Editor if Allegro is completely different. Also walmart one, are the Cadence Allegro courses worth it? I won't be paying for it and if it's worth it, I figure I might as well use the opportunity to say I know how to use two complex CAD tools.




between

Interaction between Innovus and Virtuoso through OA database

Hello,

I created a floorplan view in Virtuoso ( it contains pins and blockages). I am trying to run PnR in Innovus for floorplan created in Virtuoso. I used  set vars(oa_fp)    "Library_name cell_name view_name"   to read view from virtuoso. I am able to see pins in Innovus but not the blockages. Can i know how do i get the blockages created in virtuoso to Innovus.

Regards,
Amuu 




between

Force cell equivalence between same-footprint and same-functionality hard-macros in Conformal LEC

For a netlist vs. netlist LEC flow we have to solve the following problem:

- in the RTL code we replicate a large array of N x M all-identical hard-macros, let call them MACRO_A

- MACRO_A is pre-assembled in Innovus and contains digital parts and analog parts (bottom-up hierarchical flow)

- at top-level (full-chip) we instantiate this array of all-identical macros

- in the top-level place-and-route flow we perform ecoChangeCell to remaster the top row of this array with MACRO_B

- MACRO_B is just a copy of the original MACRO_A cell containing same pins position, same internal digital functionality and also same digital layout, only slight differences in one analog block inside the macro

- MACRO_A and MACRO_B have the same .lib file generated with the do_extract_model command at the end of the Innovus flow, they only differ in the name of the macro

- when performing post-synthesis netlist vs post-place-and-route we load .lib files of both macros in Conformal LEC

- the LEC flow fails because Conformal LEC sees only MACRO_A instantiated in the post-synthesis netlist and both MACRO_A and MACRO_B in the post-palce-and-route netlist

Since both digital functionality and STD cells layout are the same between MACRO_A and MACRO_B we don't want to keep track of this difference already at RTL stage, we just want to perform this ECO change in place-and-route and force Conformal to assume equivalence between MACRO_A and MACRO_B .

Basically what I'm searching for is something similar to the add_instance_equivalences Conformal command but that works between Golden and Revised designs on cell primitives/black-boxes .

Is this flow supported ?

Thanks in advance

Luca




between

Inconsistent behaviour of warn() between Virtuoso and Allegro

For a project, we depend on capturing warnings. This works fine in Virtuoso but behaves differently in Allegro.

In our observations

Virtuoso:

>>> warn("Hello")

*WARNING* Hello

Allegro:

>>> warn("Hello")

*WARNING* Hello

But when we capture the warning:

Virtuoso:

>>> warn("Hello") getWarn()

"Hello"

Allegro:

>>> warn("Hello") getWarn()

"*WARNING* Hello"

This is a Problem for because we put an empty String in the warn and depend on the fact that no Warning results in an empty String but on Allegro the output always begins with *WARNING*

Is there a way to make the behavior consistent in both versions?




between

Is it possible to get a diff between two coverage databases in IMC?

I'm in the process of weeding a regression test list. I have a coverage database from the full regression list and would like to diff it with the coverage database from the new reduced regression test list. If possible I would than like to trace back any buckets covered with the full list, but not with the partial list, into the original tests that covered them.

Is that possible using IMC? if not, is it possible to do from Specman itself?

(Note that we're not using vManager)

Thanks,

Avidan




between

Accurate delay measurement between two clocks

Hi,

I am currently struggling with measuring the delay between two clocks with a sufficient accuracy. The reference one is a fixed-phase clock, and the other one is a squared clock resulting of a circuit (kind of PLL) synthesis.
As I need to run a large amount of Monte-Carlo simulations in transient noise, I need to improve the simulation speed, while keeping a satisfactory delay measurement accuracy (<0.1ps), more specifically at 0V-crossings of the differential clocks. So I cannot simply set a max timestep <0.1ps as it would be far too long to simulate.
To sum up, I would need a very relaxed timestep on clock up and down levels, and a very short timestep only at rise/fall transitions.

For this purpose, I wrote a Verilog-A script
- using a timmer function to accurately emulate the reference clock 0V-crossing times (and get the related times with $abstime)
- using @(cross to get the 0V-crossing times of the synthesized clock: but this is not accurate enough (I see simulation noise around 3ps in Conservative). Indeed, the "cross" event occures at the simulation time following the effective 0V-crossing time; this could be sometimes >3ps, far not enough accurate for my purpose.
- I have tried to replace the cross with the "above" function, but it hasn't changed anything, whatever the time_tol value I put (<0.1ps for instance), the result is the same as with the "cross" function and the points are larger than >>0.1ps, weirdly.

So I have decided to give up Verilog-A to measure the delay between my two clocks.
I am currently trying to use the "delay" function of the Cadence Calculator as I guess it will "extrapolate" the time between two simulation points and therefore give a more accurate measurement of the 0V-crossing events, but when I try to compute the delay difference between the synthesized clock and the reference clock, it returns "0".

...

Could you please give me hints to dramatically improve my 0V-crossing time measurements while relaxing the simulation time?
- either by helping me in writing a more suitable Verilog-A script
- or by helping me in using the "delay" function of the calculator
- or maybe by providing me a "magic" Skill function?
Using AMS+Multithread simulator...

Thanks a lot in advance for your help and best regards.





between

Operations achieved at 290-MW Nam Ngiep 1 hydropower plant between Laos and Thailand

Kansai Electric Power Co. Inc. announces that the 290-MW Nam Ngiep 1 hydropower plant has begun commercial operations.




between

Austrade supports strong economic ties between NSW and China

Austrade has partnered with the NSW Government to deliver one of the largest business missions from Guangdong Province ever to visit Australia.



  • 2019 Latest from Austrade

between

The best blenders for smoothies, soups, and everything in between

BEST DEALS ON BLENDERS:


Today's lesson in Cooking as a Grown-Ass adult: Blenders are used for more than frozen margs in summer and collecting dust in winter.

Hot soup without a stove, coffee without a coffee maker, and whipped cream without a hand mixer are just a few of the tasks these multitasking appliances can tackle. Similar to the way the mystical Instant Pot replaces a sauté pan or slow cooker, blenders can expand your meal possibilities tenfold without the clutter of multiple machines. Read more...

More about Tech, Food, Kitchen, Mashable Shopping, and Blenders
IMAGE: Amazon

BEST OVERALL

Vitamix Professional Series 750

This classic Vitamix annihilates fruits and nuts and has presets to make just about anything.

  • Power: 1,560 watts
  • Container size: 64-ounce
  • Automated settings: smoothies, hot soups, frozen desserts, purées, self-cleaning
  • App-connected: No
$598.95 from Amazon

IMAGE: Amazon

BEST FOR MIXING DOUGH

Ninja Mega Kitchen System (BL770)

Expand to pizza or cookie dough with this food processing bowl — just ignore the noise.

  • Power: 1,500 watts
  • Pitcher size: 72-ounce
  • Automated settings: dough, blend, crush, single serve
  • App-connected: No
$149.99 from Amazon

IMAGE: Amazon

BEST BANG FOR YOUR BUCK

Calphalon Auto-Speed Blender

Novices and experts alike will appreciate the auto-adjusting speeds, screen, and long warranty.

  • Power: 1,100 watts
  • Container size: 67.6-ounce
  • Automated settings: smoothie, dip, milkshake, frozen drink
  • App-connected: No
$159.99 from Amazon

IMAGE: NutriBullet

BEST PERSONAL BLENDER

NutriBullet Balance

Track fitness goals and nutrition facts with the Bluetooth smart scale and Balance app.

  • Power: 1,200 Watts
  • Container size: 32-ounce
  • Automated settings: None
  • App-connected: Yes
$149.94 from NutriBullet

IMAGE: Amazon

BEST SMART BLENDER

Vitamix A3500

Walk-away convenience and the touchscreen are life-changing, but iPads can be bought for cheaper.

  • Power: 1,500 watts
  • Container size: 64-ounce
  • Automated settings: smoothies, hot soups, dips and spreads, frozen desserts, self-cleaning
  • App-connected: Yes
$565 from Amazon

IMAGE: Amazon

BEST HAND BLENDER

Breville Control Grip Immersion Blender

Dressing, soup, merengue, and whipped cream can achieve the perfect texture with 15 trigger speeds and an ergonomic handle.

  • Power: 280 watts
  • Pitcher size: 42-ounce
  • Automated settings: None
  • App-connected: No
$83.95 from Amazon

IMAGE: Amazon

BEST FOR WORKOUTS

Oster Blend-N-Go

A pre-gym smoothie always feels rushed, but this blending pitcher doubles as a sport bottle.

  • Power: 400 watts
  • Pitcher size: 20-ounce
  • Automated settings: None
  • App-connected: No
$19.99 from Amazon

IMAGE: Amazon

BUDGET PICK

Hamilton Beach Wave Crusher (58163)

This classic blender is great for newbies and triples as a personal blender and food processor — but you get what you pay for.

  • Power: 700 watts
  • Container size: 40-ounce
  • Automated settings: milkshake/easy clean, purée/smoothie, dice/salsa, crush ice/grate
  • App-connected: No
$59.99 from Amazon

IMAGE: Amazon

BEST FOR TRAVELING

PopBabies Personal Blender

USB charging makes this great for going off the grid or for work.

  • Power: 175 watts
  • Container size: 14-ounce
  • Automated settings: None
  • App-connected: No
$36.99 from Amazon

IMAGE: NutriBullet

BEST FOR SWITCHING UP RECIPES

NutriBullet

Though it only has one speed, you'll get two different blade options included with the set.

  • Power: 600 watts
  • Cup size(s): Two 18-ounce, one 24-ounce
$59.99 from NutriBullet

IMAGE: Amazon

BEST FOR EXTRACTING NUTRIENTS

Nutri Ninja with FreshVac Technology

Get the most nutrients and best flavors from your produce with this blender's FreshVac pump.

  • Power: 1,100 watts
  • Cup size(s): Two 24-ounce
$56.99 from Amazon

IMAGE: NutriBullet

BEST BANG FOR YOUR BUCK

Magic Bullet

A cheap, reliable blender that isn't too feature-heavy.

  • Power: 250 watts
  • Cup size(s): One 12-ounce, two 18-ounce
$39.99 from NutriBullet

IMAGE: Amazon

BEST FOR TAKING IN THE CAR

Homgeek Personal Mini Blender

With two slim sports bottles, this compact blender is a solid choice.

  • Power: 300 watts
  • Cup size(s): Two 20-ounce
$23.99 from Amazon

IMAGE: Amazon

BEST FOR CAMPING

Cozibot Travel Blender

Just because you're far from an outlet doesn't mean you need to skip your smoothie.

  • Power: 65 watts
  • Cup size(s): One 13-ounce
$34.96 from Amazon




between

The Russian Supreme Court brings clarifications to the relationship between co-owners of intellectual property

...




between

New Findings on Links between Urban Expansion and Viral Disease in Vietnam Offer Lessons for COVID-19

By James H. Spencer, Sumeet Saksena, and Jefferson Fox HONOLULU (1 April 2020)—The current COVID-19 pandemic, which started in Wuhan, China, underscores what the public health community has warned about for more than two decades—the risk of viral diseases capable of spreading from animal to human hosts. The first outbreaks of “bird flu” (highly pathogenic avian influenza―HPAI, subtype H5N1) raised similar concerns 20 years ago―concerns that have persisted with the outbreak of SARS in 2002–2004 and COVID-19 today. New outbreaks of avian influenza are also still occurring in poultry and humans, primarily in Asia but also in other parts of the world.

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.




between

UK IHC HR ebrief EU appears open-minded about pay between assignment contracts

EU appears open-minded about pay between assignment contracts Having inherited the Agency Workers Regulations 2010 on taking office, the UK Government had p...




between

Richard Branson must pick between space and planes




between

Drivers burn to death in horror N2 crash between truck and tanker

A horror crash involving a truck and a tanker carrying a flammable substance has led to the closure of the N2, near the Mtunzini Toll Plaza on the KwaZulu-Natal north coast. ......




between

European Commission aims to level the playing field between suppliers and large customers by introducing recommendations on unfair trade practices

European Commission aims to level the playing field between suppliers and large customers by introducing recommendations on unfair trade practices The European Commission recently adopted a Communication encouraging EU Member States to look at ways ...




between

Cooperation agreements between French large retailers to be reviewed by the French Competition Authority

The French Competition Authority (FCA) is entitled to give advisory opinions on any competition matter, in particular for the attention  of the French Government and the Parliament. The FCA has been recently asked to give its opinion on coopera...




between

Coronavirus has created a rift between the US and China that may take a generation ...

The novel coronavirus has destroyed lives and livelihoods in both the United States and China. But instead of bonding the two nations together to fight the pandemic, it has sent their already strained relations on a rapid downward spiral — and fanned the flames of a potentially dangerous strain of nationalism. China has been criticized at home and abroad over its handling of the virus, especially during the initial outbreak. Pushing back such criticism with increasingly fierce rhetoric, Beijing says it is merely “responding” to false accusations, particularly from the US. In March, as the pandemic raged across the globe, Chinese Foreign Ministry spokesman Zhao Lijian...




between

Across the World, Construction Workers are Caught Between Coronavirus Risk and Joblessness

A daily commute of two-and-a-half hours each way would take a toll on anyone, but for Özkan, a construction worker in Istanbul, the hardest part of his long journey is coping with his fears about what might happen after he gets home. “The conditions on our job site are deplorable, and I feel psychologically broken […]

The post Across the World, Construction Workers are Caught Between Coronavirus Risk and Joblessness appeared first on Inter Press Service.




between

Pact between KNTC and OCP Kenya heralds new era in fertiliser supply

The partnership will ensure farmers get the input not only at the correct price but also at the right time.




between

The Unseen Link Between Clean Cooking and the COVID-19 Pandemic

The COVID-19 pandemic has exacerbated inequalities and revealed to what extent current economic models are not sustainable. It has also shown that most countries are not equipped to cope with a health crisis. The World Food Program is warning that the lives and livelihoods of 265 million people in low and middle-income countries will be […]

The post The Unseen Link Between Clean Cooking and the COVID-19 Pandemic appeared first on Inter Press Service.




between

Coronavirus: COVID-19 'has exposed fundamental tensions' between EU and China

1




between

The surprising link between trade finance and gender equality -- by Steven Beck

To level the playing field in Asia and the Pacific, women-owned companies need financial backing to support their importing and exporting needs.




between

Hide and seek between merchants and police comes to halt

Rawalpindi : Merchants while lauding decision of the government for relaxing coronavirus lockdown took a sigh of relief as Eid season is around the corner. For the last few weeks specifically following the advent of the holy month of Ramazan, there were reports that merchants were treating...




between

Leprosy May Pass Between Armadillos and People

Title: Leprosy May Pass Between Armadillos and People
Category: Health News
Created: 4/28/2011 11:01:00 AM
Last Editorial Review: 4/28/2011 12:00:00 AM




between

Study Finds Direct Link Between Obesity, Heart Disease

Title: Study Finds Direct Link Between Obesity, Heart Disease
Category: Health News
Created: 5/2/2012 10:05:00 AM
Last Editorial Review: 5/2/2012 12:00:00 AM




between

No Link Found Between Playing Football in Hot Weather, Concussion Risk

Title: No Link Found Between Playing Football in Hot Weather, Concussion Risk
Category: Health News
Created: 4/28/2014 4:36:00 PM
Last Editorial Review: 4/29/2014 12:00:00 AM




between

No Link Between Anti-Smoking Drugs, Mental Health Issues: Study

Title: No Link Between Anti-Smoking Drugs, Mental Health Issues: Study
Category: Health News
Created: 4/22/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 12:00:00 AM




between

AHA News: The Often-Overlooked Connection Between Sleep Troubles and Stroke

Title: AHA News: The Often-Overlooked Connection Between Sleep Troubles and Stroke
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM




between

COMMENTARY: The Links Between COVID-19 and Diabetes, Known and Unknown

Dr Harpreet Bajaj summarizes the known and unknown links between diabetes and COVID-19, focusing on three clinical questions.




between

Oral Health-Related Quality of Life of Children: An Assessment of the Relationship between Child and Caregiver Reporting

Purpose: Oral and craniofacial conditions or diseases can impact an individual's health and quality of life. The purpose of this study was to assess the perceived oral health related quality of life (OHRQoL) of children, and evaluate the reported level of agreement between caregivers and their children.Methods: Purposive sampling was used to recruit children ages 8-15, and their caregivers from a dental clinic in a pediatric hospital for this descriptive, cross-sectional study. A modified version of a validated measure, Child Oral Health Impact Profile-Short Form (COHIP-SF), was used for a 22-item questionnaire encompassing three subscales: oral health, functional well-being, and social emotional well-being. Two additional items were included to assess child/caregiver's level of agreement. A dental chart review was also conducted to assess the child's overbite, overjet, and decayed surfaces. Data were analyzed through descriptive statistics and examined for assumptions of normality and linearity.Results: Sixty child/caregiver pairs (n=120) participated in this study. Overbite, overjet and decayed surfaces were not found to be related to any OHRQoL variable, including child/caregiver ratings and overall agreement (p>.05). Average OHRQoL scores for caregivers found to be more positive those of their children (p=.02). Agreement between caregivers and the child's gender was shown to be significant (p=.01). Female child scores differed significantly from males with respect to their caregiver responses (p=.02). Caregivers rated a higher OHRQoL for female children, thus overestimating their female child's reported OHRQoL.Conclusions: The moderate level of agreement found between children and caregivers reinforces the importance of including the child, as well as the caregiver, when assessing OHRQoL.




between

Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST

ABSTRACT

Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST.

IMPORTANCE The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time.




between

Epistatic Interplay between Type IV Secretion Effectors Engages the Small GTPase Rab2 in the Brucella Intracellular Cycle

ABSTRACT

Intracellular bacterial pathogens remodel cellular functions during their infectious cycle via the coordinated actions of effector molecules delivered through dedicated secretion systems. While the function of many individual effectors is known, how they interact to promote pathogenesis is rarely understood. The zoonotic bacterium Brucella abortus, the causative agent of brucellosis, delivers effector proteins via its VirB type IV secretion system (T4SS) which mediate biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV). Here, we show that T4SS effectors BspB and RicA display epistatic interactions in Brucella replication. Defects in rBCV biogenesis and Brucella replication caused by deletion of bspB were dependent on the host GTPase Rab2a and suppressed by the deletion of ricA, indicating a role of Rab2-binding effector RicA in these phenotypic defects. Rab2a requirements for rBCV biogenesis and Brucella intracellular replication were abolished upon deletion of both bspB and ricA, demonstrating that the functional interaction of these effectors engages Rab2-dependent transport in the Brucella intracellular cycle. Expression of RicA impaired host secretion and caused Golgi fragmentation. While BspB-mediated changes in ER-to-Golgi transport were independent of RicA and Rab2a, BspB-driven alterations in Golgi vesicular traffic also involved RicA and Rab2a, defining BspB and RicA’s functional interplay at the Golgi interface. Altogether, these findings support a model where RicA modulation of Rab2a functions impairs Brucella replication but is compensated by BspB-mediated remodeling of Golgi apparatus-associated vesicular transport, revealing an epistatic interaction between these T4SS effectors.

IMPORTANCE Bacterial pathogens with an intracellular lifestyle modulate many host cellular processes to promote their infectious cycle. They do so by delivering effector proteins into host cells via dedicated secretion systems that target specific host functions. While the roles of many individual effectors are known, how their modes of action are coordinated is rarely understood. Here, we show that the zoonotic bacterium Brucella abortus delivers the BspB effector that mitigates the negative effect on bacterial replication that the RicA effector exerts via modulation of the host small GTPase Rab2. These findings provide an example of functional integration between bacterial effectors that promotes proliferation of pathogens.




between

Synergy between Cell Surface Glycosidases and Glycan-Binding Proteins Dictates the Utilization of Specific Beta(1,3)-Glucans by Human Gut Bacteroides

ABSTRACT

The human gut microbiota (HGM) has far-reaching impacts on human health and nutrition, which are fueled primarily by the metabolism of otherwise indigestible complex carbohydrates commonly known as dietary fiber. However, the molecular basis of the ability of individual taxa of the HGM to address specific dietary glycan structures remains largely unclear. In particular, the utilization of β(1,3)-glucans, which are widespread in the human diet as yeast, seaweed, and plant cell walls, had not previously been resolved. Through a systems-based approach, here we show that the symbiont Bacteroides uniformis deploys a single, exemplar polysaccharide utilization locus (PUL) to access yeast β(1,3)-glucan, brown seaweed β(1,3)-glucan (laminarin), and cereal mixed-linkage β(1,3)/β(1,4)-glucan. Combined biochemical, enzymatic, and structural analysis of PUL-encoded glycoside hydrolases (GHs) and surface glycan-binding proteins (SGBPs) illuminates a concerted molecular system by which B. uniformis recognizes and saccharifies these distinct β-glucans. Strikingly, the functional characterization of homologous β(1,3)-glucan utilization loci (1,3GUL) in other Bacteroides further demonstrated that the ability of individual taxa to utilize β(1,3)-glucan variants and/or β(1,3)/β(1,4)-glucans arises combinatorially from the individual specificities of SGBPs and GHs at the cell surface, which feed corresponding signals to periplasmic hybrid two-component sensors (HTCSs) via TonB-dependent transporters (TBDTs). These data reveal the importance of cooperativity in the adaptive evolution of GH and SGBP cohorts to address individual polysaccharide structures. We anticipate that this fine-grained knowledge of PUL function will inform metabolic network analysis and proactive manipulation of the HGM. Indeed, a survey of 2,441 public human metagenomes revealed the international, yet individual-specific, distribution of each 1,3GUL.

IMPORTANCE Bacteroidetes are a dominant phylum of the human gut microbiota (HGM) that target otherwise indigestible dietary fiber with an arsenal of polysaccharide utilization loci (PULs), each of which is dedicated to the utilization of a specific complex carbohydrate. Here, we provide novel insight into this paradigm through functional characterization of homologous PULs from three autochthonous Bacteroides species, which target the family of dietary β(1,3)-glucans. Through detailed biochemical and protein structural analysis, we observed an unexpected diversity in the substrate specificity of PUL glycosidases and glycan-binding proteins with regard to β(1,3)-glucan linkage and branching patterns. In combination, these individual enzyme and protein specificities support taxon-specific growth on individual β(1,3)-glucans. This detailed metabolic insight, together with a comprehensive survey of individual 1,3GULs across human populations, further expands the fundamental roadmap of the HGM, with potential application to the future development of microbial intervention therapies.