Comparison of the structures of ClpC1-Ecumicin and ClpC1-Rufomycin reveals unique interaction relevant to the mode of action.

The title phospho­nate-based organic–inorganic hybrid framework, poly[bis(dimethylammonium) [(μ4-2,5-dihydroxybenzene-1,4-diphosphonato)zinc(II)]], {(C2H8N)2[Zn(C6H4O8P2)]}n, was formed unexpectedly when di­methyl­ammonium cations were formed from the in situ deca­rbonylation of the N,N-di­methyl­formamide solvent. The framework is built up from ZnO4 tetra­hedra and bridging di­phospho­nate tetra-anions to generate a three-dimensional network comprising [100] channels occupied by the (CH3)2NH2+ cations. Within the channels, an array of N—H⋯O hydrogen bonds help to establish the structure. In addition, intra­molecular O—H⋯O hydrogen bonds between the appended –OH groups of the phenyl ring and adjacent PO32− groups are observed.

The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1–ClpP1–ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD–ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 Å, β = 90.07°; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 Å resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.

People living along the coast of Peru were eating popcorn 2,000 years earlier than previously reported and before ceramic pottery was used there, according to a new paper in the Proceedings of the National Academy of Sciences.

The post Ancient popcorn discovered in Peru appeared first on Smithsonian Insider.

The US Federal Reserve has created a new group to advise on its planned faster payments service, the FedNow...

The Critical Investor discusses recent developments at the company that is exploring the Goliath Gold Project in Ontario.

Visit the aureport.com for more information and for a free newsletter

Mary Ann de Lares Norris is Chief Operating Officer of Oblong Industries. She brings her dog LouLou to Oblong's downtown LA headquarters.; Credit: Brian Watt/KPCC

KPCC recently reported on the tech world’s diversity problem. Technology firms face challenges in hiring diverse staffs of its coders, web developers and software engineers.

It’s also a challenge at nonprofits such as Southern California Public Radio,  parent of 89.3 KPCC, which has always sought to build a staff that reflects the region it serves. The section of that staff that develops the KPCC app and makes its website run is all white and mostly male.

But a small talent pool means the diversity challenge is even greater for nonprofits and even smaller tech firms.

“The first problem is that all of the people working for me are male,” says Alex Schaffert, the one female on KPCC’s tech team.  “I’m kind of focusing on maybe getting another girl into the mix.”

Schaffert can use the term “girl” because she happens to be the leader of the tech team:  KPCC’s Managing Director of Digital Strategy and Innovation. 

Why diversity is important

Schaffert recently launched the topic of diversity – or lack thereof – at a weekly meeting of her team. She expected a “stilted and awkward” discussion from the five white men on her team, but a few of them didn’t hold back.  

“Not having diversity represented on the team leaves us more susceptible to circular thinking and everyone sort of verifying each other's assumptions,” said Joel Withrow,  who was serving at the time as KPCC’s Product Manager. “It impacts the work. It limits what you’re able to build.”

Sean Dillingham, KPCC’s Design and Development Manager, said living in a diverse community is what attracted him to Los Angeles, and he wants diversity in his immediate work team, too.

“When I look at other tech companies, I will often go to their ‘about us’ page, where they’ll have a page of photos of everyone, and I am immediately turned off when I just see just a sea of white dudes, or even just a sea of dudes,” Dillingham said.

Big competition, small talent pool

Dillingham and Schaffert are currently recruiting heavily to fill two tech-savvy positions. When a reporter or editor job opens up at KPCC, Schaffert says close to 100 resumes come in.

"But if you post a programmer job, and you get three or four resumes, you may not get lucky among those resumes," she says. "There may not be a woman in there. There may not be a person of color in there."

In other words, the talent pool is already small, and the diversity challenge makes it even smaller. KPCC is competing for talent with Google and Yahoo and all the start-ups on L.A.’s Silicon Beach. 

Schaffert’s being proactive, mining LinkedIn and staging networking events to attract potential candidates. She’s also trying to make sure KPCC’s job descriptions don’t sound like some she's seen in the tech world.

"If you read between the lines, they’re really looking for someone who is male and is somewhere between 25-30 years old and likes foosball tables and free energy drinks in the refrigerator," Schaffert says. “So you read between lines, and you know that they’re not talking about me, a mother of two kids who also has a demanding career. They're talking about someone different.”

Pay vs. passion

Schaffert's challenges and approaches to dealing with them are similar to those of Mary Ann de Lares Norris, the Chief Operating Officer at Oblong Industries. Based in downtown Los Angeles and founded in 2006, the company designs operating platforms for businesses that allow teams to collaborate in real time on digital parts of a project.

“I think technology and diversity is tough,” Norris told KPCC.  She’s proud her company’s management ranks are diverse, but says only 12 percent of its engineers are female. “Pretty standard in the tech industry, but it’s not great,” Norris says. “We really strive to increase that number, and all of the other companies are also, and it's really hard.”

Like Schaffert at KPCC, Norris works hard fine-tuning job descriptions and communicating that her company values diversity and work-life balance. But sometimes, it just boils down to money.

"We have to put out offers that have competitive salaries,” Norris says, adding that she can’t compete with the major tech firms. "The Googles and the Facebooks of the world can always pay more than we can. So we attract people who are passionate about coming to work for Oblong.  And, of course, we also offer stock options."

KPCC doesn’t have the  stock options, but we’ve got plenty of passion. Could that be the secret recruiting weapon for both small tech companies and nonprofits?  

LinkedIn recently surveyed engineers about what they look for in an employer. Good pay and work-life balance were the two top draws. Slightly more women prioritized work-life balance and slightly more men chose the big bucks. 

Clinical Entrepreneurship professor Adlai Wertman says that, historically, nonprofits and small businesses actually had the upper hand over big companies in recruiting minorities and women.

"There’s a feeling that they’re safer, more caring environments, less killer environments, and we know that corporate America has been the bastion of white males," said Wertman. 

But Wertman says that advantage disappears in the tech world because of the "supply-and-demand" problem with talent. When big firms decide to focus on diversity – as some have recently — they have plenty of resources.

"They’re always going to be able to pay more, and in truth they’re getting access to students coming out of these schools in ways that we as nonprofits and small companies never will," said Wertman. 

Wertman worked 18 years as an investment banker on Wall Street, then left to head a nonprofit on L.A.’s skid row. Now he heads the Brittingham Social Enterprise Lab Enterprise Lab at USC’s Marshall School of Business. He believes that, early on, the big companies have the best shot attracting diverse tech talent. But in the long run, much of that talent will turn back to smaller firms and nonprofits.

"I think ultimately people vote with where they’re most comfortable, where 'my values align with my employer's values, and if I don’t feel those values align, then I’m going to leave,'" Wertman said. "Ultimately, I think, for a lot of women and minorities, there’s a lot of value alignment within communities that are doing good in the world." 

This content is from Southern California Public Radio. View the original story at SCPR.org.

A research update on climate change has indicated that many global risks are now assessed as stronger than predicted by the 2007 IPCC Fourth Assessment Report (AR4). The risk of large sea-level rise, extreme weather events and ocean acidification are all thought to be underestimated by the AR4.

Applying a low voltage to polluted river sediment can boost microbes’ natural ability to degrade harmful polychlorinated biphenyl (PCB) contaminants, according to a new study. The approach could be a cost-effective, sustainable strategy to bioremediate polluted sites.

Strict lockdown measures around the world has caused severe delays and logistical issues leading to worldwide PC shipments falling by 8%, technology market analyst firm Canalys said.

Despite the disruptions owing to the COVID-19 pandemic on global supply chain, Taiwanese electronics major ASUS expects a surge in demand for laptops in India once the lockdown is lifted, even as the company prepares for a couple of launches in June this year, a top company executive has said.

NPCI consecutively reported dismal figures for April 2020 for its UPI, IMPS, NETC and Bharat BillPay platforms – as AePS emerges as an outlier.

​​A majority of Jio's last reported 388 million subscribers use devices that run on KaiOS, which is different from Android or Apple’s iOS.