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The Min System Disassembles FtsZ Foci and Inhibits Polar Peptidoglycan Remodeling in Bacillus subtilis

ABSTRACT

A microfluidic system coupled with fluorescence microscopy is a powerful approach for quantitative analysis of bacterial growth. Here, we measure parameters of growth and dynamic localization of the cell division initiation protein FtsZ in Bacillus subtilis. Consistent with previous reports, we found that after division, FtsZ rings remain at the cell poles, and polar FtsZ ring disassembly coincides with rapid Z-ring accumulation at the midcell. In cells mutated for minD, however, the polar FtsZ rings persist indefinitely, suggesting that the primary function of the Min system is in Z-ring disassembly. The inability to recycle FtsZ monomers in the minD mutant results in the simultaneous maintenance of multiple Z-rings that are restricted by competition for newly synthesized FtsZ. Although the parameters of FtsZ dynamics change in the minD mutant, the overall cell division time remains the same, albeit with elongated cells necessary to accumulate a critical threshold amount of FtsZ for promoting medial division. Finally, the minD mutant characteristically produces minicells composed of polar peptidoglycan shown to be inert for remodeling in the wild type. Polar peptidoglycan, however, loses its inert character in the minD mutant, suggesting that the Min system not only is important for recycling FtsZ but also may have a secondary role in the spatiotemporal regulation of peptidoglycan remodeling.

IMPORTANCE Many bacteria grow and divide by binary fission in which a mother cell divides into two identical daughter cells. To produce two equally sized daughters, the division machinery, guided by FtsZ, must dynamically localize to the midcell each cell cycle. Here, we quantitatively analyzed FtsZ dynamics during growth and found that the Min system of Bacillus subtilis is essential to disassemble FtsZ rings after division. Moreover, a failure to efficiently recycle FtsZ results in an increase in cell size. Finally, we show that the Min system has an additional role in inhibiting cell wall turnover and contributes to the "inert" property of cell walls at the poles.




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Cerebellar ataxia, neuropathy, hearing loss, and intellectual disability due to AIFM1 mutation

Objective

To describe the clinical and molecular genetic findings in a family segregating a novel mutation in the AIFM1 gene on the X chromosome.

Methods

We studied the clinical features and performed brain MRI scans, nerve conduction studies, audiometry, cognitive testing, and clinical exome sequencing (CES) in the proband, his mother, and maternal uncle. We used in silico tools, X chromosome inactivation assessment, and Western blot analysis to predict the consequences of an AIFM1 variant identified by CES and demonstrate its pathogenicity.

Results

The proband and his maternal uncle presented with childhood-onset nonprogressive cerebellar ataxia, hearing loss, intellectual disability (ID), peripheral neuropathy, and mood and behavioral disorder. The proband's mother had mild cerebellar ataxia, ID, and mood and behavior disorder, but no neuropathy or hearing loss. The 3 subjects shared a variant (c.1195G>A; p.Gly399Ser) in exon 12 of the AIFM1 gene, which is not reported in the exome/genome sequence databases, affecting a critical amino acid for protein function involved in NAD(H) binding and predicted to be pathogenic with very high probability by variant analysis programs. X chromosome inactivation was highly skewed in the proband's mother. The mutation did not cause quantitative changes in protein abundance.

Conclusions

Our report extends the molecular and phenotypic spectrum of AIFM1 mutations. Specific findings include limited progression of neurologic abnormalities after the first decade and the coexistence of mood and behavior disorder. This family also shows the confounding effect on the phenotype of nongenetic factors, such as alcohol and drug use and side effects of medication.




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Children With Intellectual and Developmental Disabilities as Organ Transplantation Recipients

The demand for transplantable solid organs far exceeds the supply of deceased donor organs. Patient selection criteria are determined by individual transplant programs; given the scarcity of solid organs for transplant, allocation to those most likely to benefit takes into consideration both medical and psychosocial factors. Children with intellectual and developmental disabilities have historically been excluded as potential recipients of organ transplants. When a transplant is likely to provide significant health benefits, denying a transplant to otherwise eligible children with disabilities may constitute illegal and unjustified discrimination. Children with intellectual and developmental disabilities should not be excluded from the potential pool of recipients and should be referred for evaluation as recipients of solid organ transplants.




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Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016

OBJECTIVE

No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap.

RESEARCH DESIGN AND METHODS

GBD 2016 data, including prevalence and years lived with disability (YLDs), for the DRLECs of diabetic neuropathy, foot ulcer, and amputation with and without prosthesis were used. The GBD estimated prevalence using data from systematic reviews and DisMod-MR 2.1, a Bayesian meta-regression tool. YLDs were estimated as the product of prevalence estimates and disability weights for each DRLEC. We reported global and sex-, age-, region-, and country-specific estimates for each DRLEC for 1990 and 2016.

RESULTS

In 2016, an estimated 131 million people (1.8% of the global population) had DRLECs. An estimated 16.8 million YLDs (2.1% global YLDs) were caused by DRLECs, including 12.9 million (95% uncertainty interval 8.30–18.8) from neuropathy only, 2.5 million (1.7–3.6) from foot ulcers, 1.1 million (0.7–1.4) from amputation without prosthesis, and 0.4 million (0.3–0.5) from amputation with prosthesis. Age-standardized YLD rates of all DRLECs increased by between 14.6% and 31.0% from 1990 estimates. Male-to-female YLD ratios ranged from 0.96 for neuropathy only to 1.93 for foot ulcers. The 50- to 69-year-old age-group accounted for 47.8% of all YLDs from DRLECs.

CONCLUSIONS

These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations. These findings should facilitate policy makers worldwide to target strategies at populations disproportionately affected by DRLECs.




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E-scooters are a disaster for cities – but we must embrace them

Electric scooters are a nightmare. Rented by the minute, they clog up pavements and are an ungainly eyesore, but we still need them, says Donna Lu




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Biden Would Be a Disaster for Michigan

Michigan can and will recover from the devastating COVID-19 pandemic - but not if Joe Biden wins the presidential election this November. The former vice president's radical policy platform is destined to sabotage America's second economic comeback, dooming the Great Lakes State to a bleak future of perpetual economic stagnation.




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Fast fashion speeding toward environmental disaster, report warns

Study highlights industry failures and calls for shift in consumer attitudes

The fashion industry needs to fundamentally change in order to mitigate the environmental impact of fast fashion, experts have said.

Clothes rental, better recycling processes, pollution control technology and the innovative use of offcuts are among measures that could help, they said.

Continue reading...




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Gwyneth Paltrow said starring in Shallow Hal was a 'disaster' – here’s why she is right

The actor said wearing a fat suit for the 2001 movie taught her what it is like to be humiliated as an obese person. Why are TV and film characters so rarely treated with dignity and respect?

‘Disaster” is how Gwyneth Paltrow has summed up her role in the 2001 film Shallow Hal, which will surprise few people who have actually seen it. Jack Black plays Hal, a man so shallow he has to be hypnotised in order to date a fat woman, who, through his boggled eyes, he sees as a very thin woman.

The nastiness of Shallow Hal, which has long appalled critics and fans alike, was front and centre in the trailer, where Hal’s friend attempts to “rescue” him from speaking to a fat woman, Rosemary, who is, in fact, willowy Paltrow dressed in a fat suit. But because he cannot see what she looks like, he falls for her “inner beauty”. It is an uncomfortable mix – a film that pretends to preach body acceptance while simultaneously inviting laughter at bodies that don’t fit into jeans size six and under. Take the scene where she is called a “rhino”, or the one where she cannonballs into a swimming pool causing a tidal wave. The message built into the script’s DNA is simple: fat is funny; it is OK to laugh at fat people.

Continue reading...




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Obama Slams Dropping of Michael Flynn Case, Calls White House COVID-19 Response 'Absolute Chaotic Disaster': Report

Audio of a private conversation shows the 44th president's unvarnished views about the former national security adviser's case and the White House's COVID-19 response.




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James Beggs, NASA Administrator Who Resigned After Challenger Disaster, Dies at 94

Beggs was on a leave of absence from the post when the Challenger space shuttle broke apart 73 seconds after launch on Jan. 28, 1986, killing all seven aboard




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UK garden centres prepare for sales surge to end lockdown disaster

Welsh plan to reopen stores offers hope for UK-wide industry closed in prime sales season

Garden centres are preparing for a surge in plant and flower sales that could help salvage a catastrophic year for the horticulture industry.

The UK’s 2,000 garden centres and nurseries were forced to close in March because, unlike DIY chains such as B&Q and Homebase, they were not granted “essential” retailer status. The shutdown came at a critical time of year, with 70% of sales rung up in spring, forcing devastated growers to throw away millions of plants.

Continue reading...




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In a Tunnel Beneath Alaska, Scientists Race to Understand Disappearing Permafrost

What lies inside the icy cavern seems more and more like a captive, rare animal, an Earth form that might soon be lost




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School closures leave poorest pupils at huge exams disadvantage, warns Grenfell head

Poorer children taking GCSEs and A-levels next year face an "impossible situation" because they have missed so much face-to-face teaching, a leading London headmaster has warned.




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Disadvantaged pupils 'hit hardest' by coronavirus school closures

Closing schools in response to the coronavirus has "opened up a chasm" between children from disadvantaged backgrounds and the rest, according to research.




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'Planet' disappears from sight prompting surprise and suspicions that it never actually existed

What was thought to be a planet beyond our solar system appears to have disappeared, astronomers say.




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As people disappear under lockdown, goats, rats and coyotes prowl the streets

Humans can easily forget that the cities and towns they call home and frequently visit are also home to wild animals, writes Sandra E Garcia. In Wales, goats roam the streets, while in San Francisco the Coyotes have come out




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Disabled people struggle to get food and essential items during lockdown

'I'm worried about running out of food,' says Charles Bloch




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Michel Barnier laments 'disappointing' post-Brexit talks and says 'the clock is ticking' on securing deal

The EU's chief negotiator has branded progress in post-Brexit talks disappointing and warned the "clock was ticking".




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Former Chancellor Philip Hammond calls on Government to reopen economy soon or face disaster

But in one sign of a turning tide in Number 10, the UK Government is reportedly considering a proposal to allow Brits to meet up with small "bubbles" of up to 10 of their closest family or friends.




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Professor Neil Ferguson's behaviour 'plainly disappointing' but no action will be taken, Scotland Yard says

Scotland Yard has said Professor Neil Ferguson's behaviour is "plainly disappointing" but officers do not intend to take any further action.




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Tiger King: Jeff Lowe denies conspiracy that he is Carole Baskin's ex husband in disastrous Reddit AMA

Fans had speculated that Lowe could be Baskin's first husband Michael Murdock in disguise





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Transfer news LIVE: Werner to Liverpool update, Arsenal in Disasi talks, Man Utd eye Koulibaly; Chelsea gossip

Welcome to the Evening Standard's live blog covering the latest transfer news and rumours from the Premier League and beyond.




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Football could end up 'disappearing' if it does not restart, warns LaLiga president Javier Tebas

LaLiga president Javier Tebas has warned that professional football could face a bleak future if the current season is not restarted.




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Liverpool 'disappointed' by Mayor Joe Anderson's Premier League restart comments

Liverpool have released a statement declaring themselves 'disappointed' by comments from city Mayor Joe Anderson regarding efforts to resume the Premier League season.




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Spending trillions on ‘defense’ left America unprepared for real disasters

The Pentagon can't prevent a pandemic.




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How a coronavirus recession could be disastrous for Uber and Lyft drivers

People who make their living through on-demand platforms face the possibility of a recession aggravated by a drop in demand caused by coronavirus fears.




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Editorial: US healthcare must take a more proactive approach to prepare for future disasters

The COVID-19 pandemic has revealed major deficiencies and inequities in the US healthcare system, shining a spotlight on improvements that must be made to steel the country for future disasters, argues Maia.




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'Disastrous': Joko under pressure to stop villagers taking virus home

There are growing fears that Indonesian President Joko Widodo has not done enough to stop the spread of coronavirus, risking millions of lives.




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A disaster waiting to happen or a bold, evidence-based response? In Sweden, it depends who you ask

As winter fades and spring breaks over Sweden, a high-stakes experiment in self-responsibility is underway.




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Seven in 10 suspended kindergarten kids have a disability, new figures show

Advocacy groups say children are being sent home for behaviour they cannot control; staff say other students are being put at risk.




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Seven in 10 suspended kindergarten kids have a disability, new figures show

Advocacy groups say children are being sent home for behaviour they cannot control; staff say other students are being put at risk.




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Seven in 10 suspended kindergarten kids have a disability, new figures show

Advocacy groups say children are being sent home for behaviour they cannot control; staff say other students are being put at risk.




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Neville's ex-teammates Ince and Stam disagree over Man Utd chances next season

Neville's former United teammates don't agree that Ole Gunnar Solskjaer's side are currently in a position to get closer to Liverpool at the top




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‘The Nightmare Scenario’: How Coronavirus Could Make the 2020 Vote a Disaster

Trump can’t cancel the presidential election. Here’s what you should really be worrying about.




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Novak Djokovic and Dominic Thiem can disagree, as some tennis pros struggle on the breadline

As tennis stars disagree over a proposed fighting fund for players during the coronavirus shutdown, it remains clear most lower-ranked professionals struggle to make ends meet plying their trade.




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Obama Trashes Trump Over Coronavirus Response as "Chaotic Disaster"

The gloves are officially off, because Barack Obama has made his feelings known about the way his predecessor has handled the coronavirus pandemic, and the former Prez did NOT mince words. Obama was speaking with members of the Obama Alumni Ass'n,…




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Disarm Therapeutics hires Dr Alvin Shih as new President and CEO

Massachusetts-based biotech Disarm Therapeutics has hired Dr Alvin Shih as their new President and CEO.

The Cambridge, Mass.-based firm has set itself the task of creating a new class of disease-modifying therapeutics for patients with axonal degeneration, a central drive of neurological disease.

Dr Shih brings to the role a range of experiences. Having graduated with a biology degree from Vanderbilt University in 1996, Shih joined management consultancy McKinsey where he worked as a business analyst for two years.

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Justice Department Settles Allegations of Disability and Religious Discrimination Against Nashville, Tenn.

The Department today announced a settlement resolving allegations that the Metropolitan Government of Nashville and Davidson County (Metropolitan Government) violated the Fair Housing Act (FHA) and the Religious Land Use and Institutionalized Persons Act (RLUIPA) by discriminating against Teen Challenge, a Christian substance abuse treatment program.



  • OPA Press Releases

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Justice Department Sues Large Multi-Family Housing Developer Alleging Disability-Based Housing Discrimination

The Department filed a lawsuit today against JPI Construction L.P. (JPI) and six JPI-affiliated companies in U.S. District Court in Dallas for failing to provide accessible features required by the Fair Housing Act and the Americans with Disabilities Act at multi-family housing developments in Texas and other states.



  • OPA Press Releases

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Justice Department Settles Allegations of Disability Discrimination Against Town of St. John, Indiana

The Department today announced a settlement resolving allegations that the town of St. John, Ind., violated the Fair Housing Act when it denied a petition for a zoning variance based on the disability of a prospective resident.



  • OPA Press Releases

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Disaster Fraud Hotline Available to Report Flood-Related Fraud

In response to the Red River flooding in North Dakota and Minnesota and subsequent relief efforts, the National Center for Disaster Fraud is reminding members of the public to be aware of and report any instances of alleged fraudulent activity related to relief operations and funding for victims. Members of the public can report fraud, waste, abuse or allegations of mismanagement involving disaster relief operations through the Disaster Fraud Hotline at 866-720-5721, the Disaster Fraud Fax at 225-334-4707 or the Disaster Fraud e-mail at disaster@leo.gov. Individuals can also report criminal activity to the FBI at 1-800-CALL-FBI.



  • OPA Press Releases

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Justice Department Resolves Lawsuit Alleging Disability-Based Housing Discrimination at 12 Multifamily Housing Complexes in Louisville, Kentucky

The Department announced that a federal district court judge in Louisville, Ky., approved a settlement of the Department’s lawsuit alleging that those involved in the design and construction of 12 multifamily housing complexes discriminated on the basis of disability. The complexes contain more than 800 units covered by the Fair Housing Act’s accessibility provisions.



  • OPA Press Releases

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Justice Department Reaches Settlement with Philadelphia Regarding Polling Place Access for People with Disabilities

The Department announced a settlement under the Americans with Disabilities Act (ADA) with the city of Philadelphia to greatly improve accessibility for individuals with mobility disabilities at the city’s 1,200 polling places. Today’s settlement is the first settlement by the Department with a city focused solely on accessible polling places. Under the terms of the settlement, the city of Philadelphia recognizes that accessible polling places are the cornerstone of its voting accessibility program and will make its polling places accessible to persons with disabilities.



  • OPA Press Releases

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Justice Department Files Lawsuit Alleging Disability Discrimination by the City of Baltimore, Maryland

The Department filed a lawsuit in U.S. District Court in Baltimore alleging that the city of Baltimore’s zoning code discriminates against individuals with disabilities by requiring substance abuse treatment facilities to go through a burdensome “conditional ordinance” zoning process in order to locate in any zone.



  • OPA Press Releases

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Justice Department Sues Nobel Learning Communities Inc. for Discrimination Against Children with Disabilities

The Department has filed a lawsuit in U.S. District Court in Philadelphia against Nobel Learning Communities Inc. (Nobel) alleging the company violated Title III of the Americans with Disabilities Act by excluding children with autism spectrum disorders and other disabilities from its schools and programs.



  • OPA Press Releases

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Justice Department Sues Fitchburg, Mass., Housing Authority for Disability Discrimination

The Department today filed suit against the Fitchburg Housing Authority in Fitchburg, Mass., and its Executive Director Robert W. Hill alleging that they violated the Fair Housing Act when they refused to allow a tenant to transfer to a different apartment as a reasonable accommodation for her disabilities.



  • OPA Press Releases

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Justice Department Files Lawsuit Alleging Disability-based Housing Discrimination at Six Complexes in Sioux Falls, South Dakota

The Justice Department filed a lawsuit today against Equity Homes Inc, PBR LLC, BBR LLC and Shane Hartung in U.S. District Court in South Dakota for failing to provide accessible features required by the Fair Housing Act at multi-family housing developments in Sioux Falls.



  • OPA Press Releases

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Justice Department Sues Garner, North Carolina, for Disability Discrimination

The Department has filed suit against the town of Garner, N.C., and the town’s board of adjustment alleging that they violated the Fair Housing Act when they refused to allow up to eight men recovering from drug and alcohol addictions to live together as a reasonable accommodation for their disabilities.



  • OPA Press Releases

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Justice Department Resolves Lawsuit Alleging Disability-Based Housing Discrimination at Four Multifamily Housing Complexes in Spokane County, Washington

The Department announced today a settlement of a lawsuit alleging discrimination on the basis of disability in the design and construction of four multifamily housing complexes in the Spokane, Wash., area in violation of the federal Fair Housing Act.



  • OPA Press Releases