Accurate modeling of conformational energies is key to the crystal structure prediction of conformational polymorphs. Focusing on molecules XXXI and XXXII from the seventh blind test of crystal structure prediction, this study employs various electronic structure methods up to the level of domain-local pair natural orbital coupled cluster singles and doubles with perturbative triples [DLPNO-CCSD(T1)] to benchmark the conformational energies and to assess their impact on the crystal energy landscapes. Molecule XXXI proves to be a relatively straightforward case, with the conformational energies from generalized gradient approximation (GGA) functional B86bPBE-XDM changing only modestly when using more advanced density functionals such as PBE0-D4, ωB97M-V, and revDSD-PBEP86-D4, dispersion-corrected second-order Møller–Plesset perturbation theory (SCS-MP2D), or DLPNO-CCSD(T1). In contrast, the conformational energies of molecule XXXII prove difficult to determine reliably, and variations in the computed conformational energies appreciably impact the crystal energy landscape. Even high-level methods such as revDSD-PBEP86-D4 and SCS-MP2D exhibit significant disagreements with the DLPNO-CCSD(T1) benchmarks for molecule XXXII, highlighting the difficulty of predicting conformational energies for complex, drug-like molecules. The best-converged predicted crystal energy landscape obtained here for molecule XXXII disagrees significantly with what has been inferred about the solid-form landscape experimentally. The identified limitations of the calculations are probably insufficient to account for the discrepancies between theory and experiment on molecule XXXII, and further investigation of the experimental solid-form landscape would be valuable. Finally, assessment of several semi-empirical methods finds r2SCAN-3c to be the most promising, with conformational energy accuracy intermediate between the GGA and hybrid functionals and a low computational cost.

Sorghum, a short-day tropical plant, has been adapted for temperate grain production, in particular through the selection of variants at the MATURITY loci (Ma1–Ma6) that reduce photoperiod sensitivity. Ma3 encodes phytochrome B (phyB), a red/far-red photochromic biliprotein photoreceptor. The multi-domain gene product, comprising 1178 amino acids, autocatalytically binds the phytochromobilin chromophore to form the photoactive holophytochrome (Sb.phyB). This study describes the development of an efficient heterologous overproduction system which allows the production of large quantities of various holoprotein constructs, along with purification and crystallization procedures. Crystals of the Pr (red-light-absorbing) forms of NPGP, PGP and PG (residues 1–655, 114–655 and 114–458, respectively), each C-terminally tagged with His6, were successfully produced. While NPGP crystals did not diffract, those of PGP and PG diffracted to 6 and 2.1 Å resolution, respectively. Moving the tag to the N-terminus and replacing phytochromobilin with phycocyanobilin as the ligand produced PG crystals that diffracted to 1.8 Å resolution. These results demonstrate that the diffraction quality of challenging protein crystals can be improved by removing flexible regions, shifting fusion tags and altering small-molecule ligands.

Porphyromonas gingivalis is a major pathogenic oral bacterium that is responsible for periodontal disease. It is linked to chronic periodontitis, gingivitis and aggressive periodontitis. P. gingivalis exerts its pathogenic effects through mechanisms such as immune evasion and tissue destruction, primarily by secreting various factors, including cysteine proteases such as gingipain K (Kgp), gingipain R (RgpA and RgpB) and PrtH (UniProtKB ID P46071). Virulence proteins comprise multiple domains, including the pro-peptide region, catalytic domain, K domain, R domain and DUF2436 domain. While there is a growing database of knowledge on virulence proteins and domains, there was no prior evidence or information regarding the structure and biological function of the well conserved DUF2436 domain. In this study, the DUF2436 domain of PrtH from P. gingivalis (PgDUF2436) was determined at 2.21 Å resolution, revealing a noncanonical β-jelly-roll sandwich topology with two antiparallel β-sheets and one short α-helix. Although the structure of PgDUF2436 was determined by the molecular-replacement method using an AlphaFold model structure as a template, there were significant differences in the positions of β1 between the AlphaFold model and the experimentally determined PgDUF2436 structure. The Basic Local Alignment Search Tool sequence-similarity search program showed no sequentially similar proteins in the Protein Data Bank. However, DaliLite search results using structure-based alignment revealed that the PgDUF2436 structure has structural similarity Z-scores of 5.9–5.4 with the C-terminal domain of AlgF, the D4 domain of cytolysin, IglE and the extracellular domain structure of PepT2. This study has elucidated the structure of the DUF2436 domain for the first time and a comparative analysis with similar structures has been performed.

Using a 1:1 cocrystal of (E)-N-(3,4-di­fluoro­phen­yl)-1-(pyridin-4-yl)methanimine with acetic acid, C12H8F2N2·C2H4O2, we investigate the influence of F atoms introduced to the aromatic ring on promoting π–π inter­actions. The cocrystal crystallizes in the triclinic space group P1. Through crystallographic analysis and com­putational studies, we reveal the mol­ecular arrangement within this co­crystal, demonstrating the presence of hydrogen bonding between the acetic acid mol­ecule and the pyridyl group, along with π–π inter­actions between the aromatic rings. Our findings highlight the importance of F atoms in promoting π–π inter­actions without necessitating full halogenation of the aromatic ring.

3D electron diffraction (3D ED), or microcrystal electron diffraction (MicroED), has become an alternative technique for determining the high-resolution crystal structures of compounds from sub-micron-sized crystals. Here, we considered l-alanine, α-glycine and urea, which are known to form good-quality crystals, and collected high-resolution 3D ED data on our in-house TEM instrument. In this study, we present a comparison of independent atom model (IAM) and transferable aspherical atom model (TAAM) kinematical refinement against experimental and simulated data. TAAM refinement on both experimental and simulated data clearly improves the model fitting statistics (R factors and residual electrostatic potential) compared to IAM refinement. This shows that TAAM better represents the experimental electrostatic potential of organic crystals than IAM. Furthermore, we compared the geometrical parameters and atomic displacement parameters (ADPs) resulting from the experimental refinements with the simulated refinements, with the periodic density functional theory (DFT) calculations and with published X-ray and neutron crystal structures. The TAAM refinements on the 3D ED data did not improve the accuracy of the bond lengths between the non-H atoms. The experimental 3D ED data provided more accurate H-atom positions than the IAM refinements on the X-ray diffraction data. The IAM refinements against 3D ED data had a tendency to lead to slightly longer X—H bond lengths than TAAM, but the difference was statistically insignificant. Atomic displacement parameters were too large by tens of percent for l-alanine and α-glycine. Most probably, other unmodelled effects were causing this behaviour, such as radiation damage or dynamical scattering.

The axoneme, a microtubule-based array at the center of every cilium, has been the subject of structural investigations for decades, but only recent advances in cryo-EM and cryo-ET have allowed a molecular-level interpretation of the entire complex to be achieved. The unique properties of the nine doublet microtubules and central pair of singlet microtubules that form the axoneme, including the highly decorated tubulin lattice and the docking of massive axonemal complexes, provide opportunities and challenges for sample preparation, 3D reconstruction and atomic modeling. Here, the approaches used for cryo-EM and cryo-ET of axonemes are reviewed, while highlighting the unique opportunities provided by the latest generation of AI-guided tools that are transforming structural biology.

The expansive scientific software ecosystem, characterized by millions of titles across various platforms and formats, poses significant challenges in maintaining reproducibility and provenance in scientific research. The diversity of independently developed applications, evolving versions and heterogeneous components highlights the need for rigorous methodologies to navigate these complexities. In response to these challenges, the SBGrid team builds, installs and configures over 530 specialized software applications for use in the on-premises and cloud-based computing environments of SBGrid Consortium members. To address the intricacies of supporting this diverse application collection, the team has developed the Capsule Software Execution Environment, generally referred to as Capsules. Capsules rely on a collection of programmatically generated bash scripts that work together to isolate the runtime environment of one application from all other applications, thereby providing a transparent cross-platform solution without requiring specialized tools or elevated account privileges for researchers. Capsules facilitate modular, secure software distribution while maintaining a centralized, conflict-free environment. The SBGrid platform, which combines Capsules with the SBGrid collection of structural biology applications, aligns with FAIR goals by enhancing the findability, accessibility, interoperability and reusability of scientific software, ensuring seamless functionality across diverse computing environments. Its adaptability enables application beyond structural biology into other scientific fields.

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.

Molecular structures can be determined in vitro and in situ with cryo-electron microscopy (cryo-EM). Specimen preparation is a major obstacle in cryo-EM. Typical sample preparation is orders of magnitude slower than biological processes. Time-resolved cryo-EM (TR-cryo-EM) can capture short-lived states. Here, Cryo-EM sample preparation with light-activated molecules (C-SPAM) is presented, an open-source, photochemistry-coupled device for TR-cryo-EM that enables millisecond resolution and tunable timescales across broad biological applications.

This paper uses deep learning to present a proof-of-concept for data-driven chemistry in single-molecule magnets (SMMs). Previous discussions within SMM research have proposed links between molecular structures (crystal structures) and single-molecule magnetic properties; however, these have only interpreted the results. Therefore, this study introduces a data-driven approach to predict the properties of SMM structures using deep learning. The deep-learning model learns the structural features of the SMM molecules by extracting the single-molecule magnetic properties from the 3D coordinates presented in this paper. The model accurately determined whether a molecule was a single-molecule magnet, with an accuracy rate of approximately 70% in predicting the SMM properties. The deep-learning model found SMMs from 20 000 metal complexes extracted from the Cambridge Structural Database. Using deep-learning models for predicting SMM properties and guiding the design of novel molecules is promising.

Evidence that the electronic structure of atoms persists in molecules to a much greater extent than has been usually admitted is presented. This is achieved by resorting to N-electron real-space descriptors instead of one- or at most two-particle projections like the electron or exchange-correlation densities. Here, the 3N-dimensional maxima of the square of the wavefunction, the so-called Born maxima, are used. Since this technique is relatively unknown to the crystallographic community, a case-based approach is taken, revisiting first the Born maxima of atoms in their ground state and then some of their excited states. It is shown how they survive in molecules and that, beyond any doubt, the distribution of electrons around an atom in a molecule can be recognized as that of its isolated, in many cases excited, counterpart, relating this fact with the concept of energetic promotion. Several other cases that exemplify the applicability of the technique to solve chemical bonding conflicts and to introduce predictability in real-space analyses are also examined.

In the structure of the title co-crystal, C3H3N3O2·C5H8N2, the components are linked by a set of directional O—H⋯N, N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds to yield a two-dimensional mono-periodic arrangement. The structure propagates in the third dimension by extensive π–π stacking inter­actions of nearly parallel mol­ecules of the two components, following an alternating sequence. The primary structure-defining inter­action is very strong oxime-OH donor to pyrazole-N acceptor hydrogen bond [O⋯N = 2.587 (2) Å], while the significance of weaker hydrogen bonds and π–π stacking inter­actions is comparable. The distinct structural roles of different kinds of inter­actions agree with the results of a Hirshfeld surface analysis and calculated inter­action energies. The title compound provides insights into co-crystals of active agrochemical mol­ecules and features the rational integration in one structure of a fungicide, C3H3N3O2, and a second active component, C5H8N2, known for alleviation the toxic effects of fungicides on plants. The material appears to be well suited for practical uses, being non-volatile, air-stable, water-soluble, but neither hygroscopic nor efflorescent.

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 Federal Trade Commission (FTC) has...

New State food rules recently put in place are expected to enforce safe food handling and reduce transmission of food-borne illness.

A new County Solid Waste Franchise with Republic Services (formerly known as GDS), effective July 1, is bringing expanded recycling, new fee schedule, services.

The U.S. Supreme Court sided with students on Wednesday, ruling that a former cheerleader's online F-bombs about her school is protected speech under the First Amendment.

By an 8-1 vote, the court declared that school administrators do have the power to punish student speech that occurs online or off campus if it genuinely disrupts classroom study. But the justices concluded that a few swear words posted online from off campus, as in this case, did not rise to the definition of disruptive.

"While public schools may have a special interest in regulating some off-campus student speech, the special interests offered by the school are not sufficient to overcome B. L.'s interest in free expression in this case," Justice Stephen Breyer wrote for the court's majority.

At issue in the case was a series of F-bombs issued in 2017 on Snapchat by Brandi Levy, then a 14-year-old high school cheerleader who failed to win a promotion from the junior varsity to the varsity cheerleading term at her Pennsylvania school.

"I was really upset and frustrated at everything," she said in an interview with NPR in April. So she posted a photo of herself and a friend flipping the bird to the camera, along with a message that said, "F*** the school ... F*** cheer, F*** everything."

Suspended from the team for what was considered disruptive behavior, Brandi and her parents went to court. They argued that the school had no right to punish her for off-campus speech, whether it was posted online while away from school, as in this case, or spoken out loud at a Starbucks across the street from school.

A federal appeals court agreed with her, declaring that school officials have no authority to punish students for speech that occurs in places unconnected to the campus.

The decision marked the first time that an appeals court issued such a broad interpretation of the Supreme Court's landmark student speech decision more then a half century ago. Back then, in a case involving students suspended for wearing black armbands to school to protest the Vietnam War, the court ruled that students do have free speech rights under the Constitution, as long as the speech is not disruptive to the school.

Although Brandi Levy is now in college, the school board in Mahanoy, Pa., appealed to the Supreme Court, contending that disruption can come from outside the campus but still have serious effects on campus. It pointed to laws in 47 states that require schools to enforce anti-bullying and anti-harassment policies.

The high court, however, focused on the facts in Levy's case, concluding that while her posts were less than admirable, they did not meet the test of being disruptive.

"We do not believe the special characteristics that give schools additional license to regulate student speech always disappear when a school regulates speech that takes place off campus," Breyer wrote. "The school's regulatory interests remain significant in some off-campus circumstances."

In a concurring opinion, Justice Samuel Alito wrote: "If today's decision teaches any lesson, it must be that the regulation of many types of off-premises student speech raises serious First Amendment concerns, and school officials should proceed cautiously before venturing into this territory."

In a dissent, Justice Clarence Thomas wrote that the school was right to suspend Levy because students like her "who are active in extracurricular programs have a greater potential, by virtue of their participation, to harm those programs."

"For example, a profanity-laced screed delivered on social media or at the mall has a much different effect on a football program when done by a regular student than when done by the captain of the football team," Thomas wrote. "So, too, here."

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

A review of the available evidence underscores the safety of the federal childhood immunization schedule, says a new report from the Institute of Medicine.

A series of educational modules has been developed by the National Academies of Sciences, Engineering, and Medicine to help students in professional schools – law, public policy, medicine, journalism, and business – understand science and its role in decision making.

The U.S. Environmental Protection Agency has issued a proposed rule for strengthening transparency in regulatory science (April 30, 2018, 83 Federal Register 18768), which stipulates that EPA will ensure that the data and models underlying the pivotal science that informs significant regulatory actions are made publicly available, in a format that allows for outside analysis and validation.

To detect soreness in Tennessee walking horses, only veterinarians should administer inspections at shows, a new report from the National Academies of Sciences, Engineering, and Medicine recommends.

The ruling by U.S. District Judge John Koeltl in Manhattan on Friday came in a closely watched lawsuit that tested the ability of Internet Archive to lend out the works of writers and publishers protected by U.S. copyright laws.

The EU's Digital Services Act is one of the most ambitious pieces of legislation on controlling online content since the advent of social media, setting major obligations on how platforms deal with free speech. Meta, TikTok, Twitter, and others have to invest heavily in building compliance teams to meet the new rules.

DNA, our genetic material, normally has the structure of a twisted rope ladder. Experts call this structure a double helix. Among other things, it is stabilized by stacking forces between base pairs. Scientists at the Technical University of Munich (TUM) have succeeded at measuring these forces for the very first time on the level of single base pairs. This new knowledge could help to construct precise molecular machines out of DNA.

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The companies will have six months to demonstrate their compliance with their obligations and can be fined up to 10% of their annual global turnover for DMA violations.

TikTok has been fined $368 million by European regulators for breaching data privacy rules and failing to protect children's privacy. The investigation found that the app's sign-up process for teen users made their accounts public by default, posing a risk to underage users. The "family pairing" feature also allowed adults to turn on direct messaging for users aged 16 and 17 without their consent.

The European Commission in September opened investigations to assess whether Microsoft's Bing, Edge and Microsoft Advertising as well as Apple's iMessage should be subject to the Digital Markets Act (DMA).

The draft AI rules have to be agreed by the European Parliament and European Union member states. They have so far been discussed three times in trilogues, which are meetings between parliament and EU states to thrash out the final versions of laws.

The Consumer Financial Protection Bureau's proposal would subject companies like Alphabet, Apple, PayPal and Block's CashApp to bank-like supervision, with CFPB examiners inspecting their privacy protections, executives' conduct and compliance with laws barring unfair and deceptive practices.

The use of the technology will also require individual's consent, the CAC said in a statement. It added that non-biometric identification solutions should be favored over facial recognition in cases where such methods are equally effective.

It offers centralized request management, omnichannel integration, self-service capabilities, enhanced visibility for business partners, employee training and tools, powerful analytics capabilities, seamless integration with existing systems, and comprehensive service offerings.

WIPOTEC-OCS recently debuted a groundbreaking multi-function metal detection-checkweigher-vision module.

The Finnish food tech company Gold&Green Foods is expanding beyond the meat replacement category with the launch of Gold&Green Protein Granules and Protein Flakes.

The design is intended to offer bakery customers faster installation.

Process equipment manufacturer Gericke USA, Somerset, NJ, has introduced the Turbo Compact Mixing (TCM) module.

The Turbo Compact Mixing (TCM) module from process equipment manufacturer Gericke USA, Somerset, NJ, meets ATEX requirements for operation in hazardous environments. 

HANTEMP Controls has unveiled a new line of stainless steel control valves & modules for pressure, temperature, and liquid control.

Are you thinking about restocking your packaging supplies? If you are, then you have a lot to think about before making the investment. 

Founded in 2017, Schedule Engine is a customer service support solution for home service contractors.

The American Supply Association (ASA) recently joined the Alliance for Water Efficiency in its appeal to the United States Department of Energy related to allowable flow-rate changes for multi-head showers, and the subsequent negative affects it will have on business operations for ASA members, as well as overall negative water-efficiency consequences that will result.

The new Market District Apartments in Ohio City will be located near the historic West Side Market, the oldest operating indoor/outdoor market space in Cleveland. Currently, the 13-story development is the largest sustainable, wood-constructed building in the country. Among other facilities, the new 385-unit structure encompasses a first-floor retail space, residential suites on floors two through seven and luxury penthouse suites on the ninth floor, as well as amenity space, including a large rental hall.

As part of the rulemaking process, the agency will seek and consider input from a ride range of stakeholders and the public at-large as it works to propose and finalize its rule.

The proposed rule would require employers to develop an injury and illness prevention plan to control heat hazards in workplaces affected by excessive heat.

The rule updates the current standard by improving the amount and quality of information on labels and safety data sheets. Updates take effect on July 19, 2024.

OSHA encourages public participation in the rulemaking process.

Currently designated as NFPA 660: Standard for Combustible Dusts, the all-encompassing standard will be completed in 2024 and likely released in late 2024/early 2025.

Rules are so easy to make that safety offices are often accused of being a “Rule Mill” because they continuously produce their rule-of-the month. Why do we create so many rules? One particular cog in our mill that causes us to create rules is incidents. When we suffer an incident, we want to throw every tool in the arsenal to keep it from happening again.

The U.S. Supreme Court’s June 2022 overturn of 1973 Roe v Wade has emboldened states to propose “fetal personhood” laws. What does this mean for proposed rulemaking for blood lead levels?

Rulemaking process for the Pregnant Workers Fairness Act includes workplace PPE, and OSH professionals should be paying attention.