A molecular device for the redox quality control of GroEL/ES substrates.

Hsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these chaperonins promote folding remain unsolved. Here, we report that the bacterial Hsp60 chaperonin GroEL forms a stable, functionally relevant complex with the chaperedoxin CnoX, a protein combining a chaperone and a redox function. Binding of GroES (Hsp10 cofactor) to GroEL induces CnoX release. Cryoelectron microscopy provided crucial structural information on the GroEL-CnoX complex, showing that CnoX binds GroEL outside the substrate-binding site via a highly conserved C-terminal α-helix. Furthermore, we identified complexes in which CnoX, bound to GroEL, forms mixed disulfides with GroEL substrates, indicating that CnoX likely functions as a redox quality-control plugin for GroEL. Proteins sharing structural features with CnoX exist in eukaryotes, suggesting that Hsp60 molecular plugins have been conserved through evolution.

Publisher Correction: c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

In the version of this article initially published, the Supplementary Data file was an incorrect version. The correct version is now provided. The error has been corrected in the HTML and PDF version of the article.

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (malaria), TH2 cells (allergy) and TH17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in TH1 and TH2 responses, TH17 cell-mediated pathology was reduced in this context, with an accompanying decrease in TH17 cells and increase in Foxp3+ regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf transcription-factor network, including enhanced activity of NFAT; this led to the identification and validation of c-Maf as a negative regulator of IL-2. The decreased expression of the gene encoding the transcription factor RORγt (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained the in vivo observations. Thus, c-Maf is a positive and negative regulator of the expression of cytokine-encoding genes, with context-specific effects that allow each immune response to occur in a controlled yet effective manner.

Extracellular chaperones and proteostasis.

There exists a family of currently untreatable, serious human diseases that arise from the inappropriate misfolding and aggregation of extracellular proteins. At present our understanding of mechanisms that operate to maintain proteostasis in extracellular body fluids is limited, but it has significantly advanced with the discovery of a small but growing family of constitutively secreted extracellular chaperones. The available evidence strongly suggests that these chaperones act as both sensors and disposal mediators of misfolded proteins in extracellular fluids, thereby normally protecting us from disease pathologies. It is critically important to further increase our understanding of the mechanisms that operate to effect extracellular proteostasis, as this is essential knowledge upon which to base the development of effective therapies for some of the world's most debilitating, costly, and intractable diseases.

Origins of structural and electronic transitions in disordered silicon.

Structurally disordered materials pose fundamental questions1-4, including how different disordered phases ('polyamorphs') can coexist and transform from one phase to another5-9. Amorphous silicon has been extensively studied; it forms a fourfold-coordinated, covalent network at ambient conditions and much-higher-coordinated, metallic phases under pressure10-12. However, a detailed mechanistic understanding of the structural transitions in disordered silicon has been lacking, owing to the intrinsic limitations of even the most advanced experimental and computational techniques, for example, in terms of the system sizes accessible via simulation. Here we show how atomistic machine learning models trained on accurate quantum mechanical computations can help to describe liquid-amorphous and amorphous-amorphous transitions for a system of 100,000 atoms (ten-nanometre length scale), predicting structure, stability and electronic properties. Our simulations reveal a three-step transformation sequence for amorphous silicon under increasing external pressure. First, polyamorphic low- and high-density amorphous regions are found to coexist, rather than appearing sequentially. Then, we observe a structural collapse into a distinct very-high-density amorphous (VHDA) phase. Finally, our simulations indicate the transient nature of this VHDA phase: it rapidly nucleates crystallites, ultimately leading to the formation of a polycrystalline structure, consistent with experiments13-15 but not seen in earlier simulations11,16-18. A machine learning model for the electronic density of states confirms the onset of metallicity during VHDA formation and the subsequent crystallization. These results shed light on the liquid and amorphous states of silicon, and, in a wider context, they exemplify a machine learning-driven approach to predictive materials modelling.

Regulation of intestinal immunity and tissue repair by enteric glia.

Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease8. Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ-EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ-EGC-CXCL10 axis in immune response and tissue repair after infectious challenge.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

Burkitt lymphoma risk shows geographic and temporal associations with Plasmodium falciparum infections in Uganda, Tanzania, and Kenya.

Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, Plasmodium falciparum, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of P. falciparum infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative P. falciparum exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime P. falciparum infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual P. falciparum infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to P. falciparum malaria and support emphasizing the link between malaria and eBL.

The Dual Roles of Clusterin in Extracellular and Intracellular Proteostasis.

Clusterin (CLU) was the first reported secreted mammalian chaperone and impacts on serious diseases associated with inappropriate extracellular protein aggregation. Many studies have described intracellular CLU in locations outside the secretory system and recent work has shown that CLU can be released into the cytosol during cell stress. In this article, we critically evaluate evidence relevant to the proposed origins of cellular CLU found outside the secretory system, and advance the hypothesis that the cytosolic release of CLU induced by stress serves to facilitate the trafficking of misfolded proteins to the proteasome and autophagy for degradation. We also propose future research directions that could help establish CLU as a unique chaperone performing critical and synergic roles in both intracellular and extracellular proteostasis.

Divergent evolution of extreme production of variant plant monounsaturated fatty acids.

Metabolic extremes provide opportunities to understand enzymatic and metabolic plasticity and biotechnological tools for novel biomaterial production. We discovered that seed oils of many Thunbergia species contain up to 92% of the unusual monounsaturated petroselinic acid (18:1Δ6), one of the highest reported levels for a single fatty acid in plants. Supporting the biosynthetic origin of petroselinic acid, we identified a Δ6-stearoyl-acyl carrier protein (18:0-ACP) desaturase from Thunbergia laurifolia, closely related to a previously identified Δ6-palmitoyl-ACP desaturase that produces sapienic acid (16:1Δ6)-rich oils in Thunbergia alata seeds. Guided by a T. laurifolia desaturase crystal structure obtained in this study, enzyme mutagenesis identified key amino acids for functional divergence of Δ6 desaturases from the archetypal Δ9-18:0-ACP desaturase and mutations that result in nonnative enzyme regiospecificity. Furthermore, we demonstrate the utility of the T. laurifolia desaturase for the production of unusual monounsaturated fatty acids in engineered plant and bacterial hosts. Through stepwise metabolic engineering, we provide evidence that divergent evolution of extreme petroselinic acid and sapienic acid production arises from biosynthetic and metabolic functional specialization and enhanced expression of specific enzymes to accommodate metabolism of atypical substrates.

Unravelling Guest Dynamics in Crystalline Molecular Organics Using 2H Solid-State NMR and Molecular Dynamics Simulation.

2H solid-state NMR and atomistic molecular dynamics (MD) simulations are used to understand the disorder of guest solvent molecules in two cocrystal solvates of the pharmaceutical furosemide. Traditional approaches to interpreting the NMR data fail to provide a coherent model of molecular behavior and indeed give misleading kinetic data. In contrast, the direct prediction of the NMR properties from MD simulation trajectories allows the NMR data to be correctly interpreted in terms of combined jump-type and libration-type motions. Time-independent component analysis of the MD trajectories provides additional insights, particularly for motions that are invisible to NMR. This allows a coherent picture of the dynamics of molecules restricted in molecular-sized cavities to be determined.

Testing predictive coding theories of autism spectrum disorder using models of active inference.

Several competing neuro-computational theories of autism have emerged from predictive coding models of the brain. To disentangle their subtly different predictions about the nature of atypicalities in autistic perception, we performed computational modelling of two sensorimotor tasks: the predictive use of manual gripping forces during object lifting and anticipatory eye movements during a naturalistic interception task. In contrast to some accounts, we found no evidence of chronic atypicalities in the use of priors or weighting of sensory information during object lifting. Differences in prior beliefs, rates of belief updating, and the precision weighting of prediction errors were, however, observed for anticipatory eye movements. Most notably, we observed autism-related difficulties in flexibly adapting learning rates in response to environmental change (i.e., volatility). These findings suggest that atypical encoding of precision and context-sensitive adjustments provide a better explanation of autistic perception than generic attenuation of priors or persistently high precision prediction errors. Our results did not, however, support previous suggestions that autistic people perceive their environment to be persistently volatile.

Community and health worker perspectives on malaria in Meghalaya, India: covering the last mile of elimination by 2030.

BACKGROUND: Malaria remains a public health problem in regions of Northeastern India because of favourable bio-geographic transmission conditions, poor access to routine healthcare, and inadequate infrastructure for public health and disease prevention. This study was undertaken to better understand community members' and health workers' perceptions of malaria, as well as their knowledge, attitudes, and prevention practices related to the disease in Meghalaya state. METHODS: The study included participants from three malaria endemic districts: West Khasi Hills, West Jaiñtia Hills, and South Garo Hills from 2019 to 2021. A total of 82 focus group discussions (FGD) involving 694 community members and 63 in-depth interviews (IDI) with health personnel and traditional healers residing within the three districts were conducted. A thematic content analysis approach was employed, using NVivo12 software for data management. RESULTS: Most participants reported a perceived reduction in malaria during recent years, attributing this to changes in attitudes and behaviours in health seeking, and to more effective government interventions. Local availability of testing and treatment, and an improved, more responsive health system contributed to changing attitudes. Long-lasting insecticidal nets (LLINs) were largely preferred over indoor residual spraying (IRS), as LLINs were perceived to be effective and more durable. Community members also reported using personal protective measures such as applying repellents, burning neem tree leaves, straw/egg trays, wearing long sleeve clothes, and applying ointments or oils to protect themselves from mosquito bites. While most participants acknowledged the role of mosquitoes in malaria transmission, other conditions that are not mosquito-borne were also attributed to mosquitoes by some participants. The communities surveyed have largely shifted from seeking treatment for malaria from traditional healers to using public facilities, although some participants reported switching between the two or using both simultaneously. Improved understanding of cerebral malaria, which some participants previously attributed to mental illness due to 'bad spirits', is an example of how cultural and ritualistic practices have changed. CONCLUSION: The findings reveal diverse perceptions among community members regarding malaria, its prevention, practices to prevent mosquito-transmitted diseases, and their opinions about the healthcare system. A key finding was the shift in malaria treatment-seeking preferences of community members from traditional healers to the public sector. This shift highlights the changing dynamics and increasing acceptance of modern healthcare practices for malaria treatment and prevention within tribal and/or indigenous communities. By recognizing these evolving attitudes, policymakers and healthcare providers can better tailor their interventions and communication strategies to more effectively address ongoing needs and concerns as India faces the 'last mile' in malaria elimination.

COVID-19 passenger screening to reduce travel risk and translocation of disease.

Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.

Computational predictions of interfacial tension, surface tension, and surfactant adsorption isotherms.

All-atom (AA) molecular dynamics (MD) simulations are employed to predict interfacial tensions (IFT) and surface tensions (ST) of both ionic and non-ionic surfactants. The general AMBER force field (GAFF) and variants are examined in terms of their performance in predicting accurate IFT/ST, γ, values for chosen water models, together with the hydration free energy, ΔGhyd, and density, ρ, predictions for organic bulk phases. A strong correlation is observed between the quality of ρ and γ predictions. Based on the results, the GAFF-LIPID force field, which provides improved ρ predictions is selected for simulating surfactant tail groups. Good γ predictions are obtained with GAFF/GAFF-LIPID parameters and the TIP3P water model for IFT simulations at a water-triolein interface, and for GAFF/GAFF-LIPID parameters together with the OPC4 water model for ST simulations at a water-vacuum interface. Using a combined molecular dynamics-molecular thermodynamics theory (MD-MTT) framework, a mole fraction of C12E6 molecule of 1.477 × 10-6 (from the experimental critical micelle concentration, CMC) gives a simulated surface excess concentration, ΓMAX, of 76 C12E6 molecules at a 36 nm2 water-vacuum surface (3.5 × 10-10 mol cm-2), which corresponds to a simulated ST of 35 mN m-1. The results compare favourably with an experimental ΓMAX of C12E6 of 3.7 × 10-10 mol cm-2 (80 surfactants for a 36 nm2 surface) and experimental ST of C12E6 of 32 mN m-1 at the CMC.

SARS-CoV-2 Inactivation on Hard Non-porous Airplane Cabin Material Surfaces was Limited After Exposure to Far UV-C (222 nm) Radiation.

AIMS: To test the efficacy of 222 nm Far UV-C for surface disinfection of SARS-CoV-2 on inanimate surfaces from airplane cabins. METHODS AND RESULTS: Two far ultraviolet (UV-C) irradiation light systems were evaluated for disinfection of SARS-CoV-2. Materials used for carriers (test surfaces) included polished stainless steel and used airplane materials including seatbelt latches, window dust covers, sidewall laminates, and tray tables. CONCLUSIONS: While demonstrating reasonable efficacy under some experimental conditions, the data indicated that 222 nm Far UV-C disinfection alone does not reliably provide a 3 log10 or 99.9% reduction of SARS-CoV-2 on inanimate surfaces from an airplane cabin. An Ushio (Cypress, CA) 1.7" x 2.3" Care222® 12W 222nm BI lamp module tested in triplicate at a low (⁓ 1.5 mJ cm-2), medium (⁓ 3.0 mJ cm-2), and high (⁓ 6 to 9 mJ cm-2) fluence did not provide a ≥ 3 log10 or 99.9% reduction of SARS-CoV-2. The reduction of SARS-CoV-2 was greatest on stainless steel. The result was a log10 reduction of 2.83, 1.33, 2.58, and 2.21 logs for virus samples containing saline, saline with 2.5 mg BSA, saline with 0.25 mg BSA, and artificial saliva respectively at a dosage of 5 to 9 mJ cm-2. The log10 reduction of SARS-CoV-2 in saline with 2.5 mg bovine serum albumin was lowest with 1.33 for stainless steel, 0.93 for belt latch, and 0.61 for tray table at a dosage of 5 to 6 mJ cm-2.The second UV lighting system tested was a prototype mobile wand with a built-in short-pass filtered krypton-chloride cylindrical lamp. One pass of the wand over a tray holding carriers inoculated with SARS-CoV-2 in artificial saliva at a rate of approximately 1 foot (1') per second (sec) exposed the carriers to 7.3 mJ cm-2. The log10 reductions determined for the single pass were 2.97, 3.75, 1.78, 1.91, and 1.28 logs for stainless steel, belt latch, dust cover, sidewall, and tray table respectively. Two passes of the wand generated 17.2 mJ cm-2 and resulted in log10 reductions of 4.04, 3.74, 4.24, 3.68, and 1.66 logs for stainless steel, belt latch, dust cover, sidewall, and tray table respectively. The combination of higher fluence from multiple passes of the wand, the close proximity (10 cm wand to the carrier), the exposure to elevated temperatures up to 35°C, and ozone from the bulb being blown directly onto the carriers contributed to effective viral inactivation on all surfaces except the airplane tray table. The impact of temperature and ozone on viral inactivation should be determined for future testing of the 222 nm UV-C wand.

Clusterin Neutralizes the Inflammatory and Cytotoxic Properties of Extracellular Histones in Sepsis.

Rationale: Extracellular histones, released into the surrounding environment during extensive cell death, promote inflammation and cell death, and these deleterious roles have been well documented in sepsis. Clusterin (CLU) is a ubiquitous extracellular protein that chaperones misfolded proteins and promotes their removal. Objectives: We investigated whether CLU could protect against the deleterious properties of histones. Methods: We assessed CLU and histone expression in patients with sepsis and evaluated the protective role of CLU against histones in in vitro assays and in vivo models of experimental sepsis. Measurements and Main Results: We show that CLU binds to circulating histones and reduces their inflammatory, thrombotic, and cytotoxic properties. We observed that plasma CLU levels decreased in patients with sepsis and that the decrease was greater and more durable in nonsurvivors than in survivors. Accordingly, CLU deficiency was associated with increased mortality in mouse models of sepsis and endotoxemia. Finally, CLU supplementation improved mouse survival in a sepsis model. Conclusions: This study identifies CLU as a central endogenous histone-neutralizing molecule and suggests that, in pathologies with extensive cell death, CLU supplementation may improve disease tolerance and host survival.

The role of prediction and visual tracking strategies during manual interception: An exploration of individual differences.

The interception (or avoidance) of moving objects is a common component of various daily living tasks; however, it remains unclear whether precise alignment of foveal vision with a target is important for motor performance. Furthermore, there has also been little examination of individual differences in visual tracking strategy and the use of anticipatory gaze adjustments. We examined the importance of in-flight tracking and predictive visual behaviors using a virtual reality environment that required participants (n = 41) to intercept tennis balls projected from one of two possible locations. Here, we explored whether different tracking strategies spontaneously arose during the task, and which were most effective. Although indices of closer in-flight tracking (pursuit gain, tracking coherence, tracking lag, and saccades) were predictive of better interception performance, these relationships were rather weak. Anticipatory gaze shifts toward the correct release location of the ball provided no benefit for subsequent interception. Nonetheless, two interceptive strategies were evident: 1) early anticipation of the ball's onset location followed by attempts to closely track the ball in flight (i.e., predictive strategy); or 2) positioning gaze between possible onset locations and then using peripheral vision to locate the moving ball (i.e., a visual pivot strategy). Despite showing much poorer in-flight foveal tracking of the ball, participants adopting a visual pivot strategy performed slightly better in the task. Overall, these results indicate that precise alignment of the fovea with the target may not be critical for interception tasks, but that observers can adopt quite varied visual guidance approaches.

Photon Upconversion in a Vapor Deposited 2D Inorganic-Organic Semiconductor Heterostructure.

Energy transfer processes may be engineered in van der Waals heterostructures by taking advantage of the atomically abrupt, Å-scale, and topologically tailorable interfaces within them. Here, we prepare heterostructures comprised of 2D WSe2 monolayers interfaced with dibenzotetraphenylperiflanthene (DBP)-doped rubrene, an organic semiconductor capable of triplet fusion. We fabricate these heterostructures entirely through vapor deposition methods. Time-resolved and steady-state photoluminescence measurements reveal rapid subnanosecond quenching of WSe2 emission by rubrene and fluorescence from guest DBP molecules at 612 nm (λexc = 730 nm), thus providing clear evidence of photon upconversion. The dependence of the upconversion emission on excitation intensity is consistent with a triplet fusion mechanism, and maximum efficiency (linear regime) of this process occurs at threshold intensities as low as 110 mW/cm2, which is comparable to the integrated solar irradiance. This study highlights the potential for advanced optoelectronic applications employing vdWHs which leverage strongly bound excitons in monolayer TMDs and organic semiconductors.

Protein target highlights in CASP15: Analysis of models by structure providers.

We present an in-depth analysis of selected CASP15 targets, focusing on their biological and functional significance. The authors of the structures identify and discuss key protein features and evaluate how effectively these aspects were captured in the submitted predictions. While the overall ability to predict three-dimensional protein structures continues to impress, reproducing uncommon features not previously observed in experimental structures is still a challenge. Furthermore, instances with conformational flexibility and large multimeric complexes highlight the need for novel scoring strategies to better emphasize biologically relevant structural regions. Looking ahead, closer integration of computational and experimental techniques will play a key role in determining the next challenges to be unraveled in the field of structural molecular biology.