Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody

The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120–gp41)₃ trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5’s tyrosine-sulfated amino (N) terminus, release of the gp41 fusion peptide and fusion. We present 3.3 Å and 3.5 Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120–gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral–host cell membrane fusion

Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

The crucial role of plasmid-encoded protein Pgp3 in Chlamydia pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient C. muridarum mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of C. trachomatis Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed C. muridarum transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient C. muridarum. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection

Middle Jurassic terrestrial environmental and floral changes linked to volcanism: Evidence from the Qinghai Tibet Plateau, China

The breakup of Pangaea and the rapid opening of the Ligurian and Central Atlantic oceans during the Middle Jurassic resulted in widespread volcanism accompanied by significant shifts in global environments, climates, and floras. Although major volcanism is a plausible driver of such global changes, linking these phenomena in the Middle Jurassic is hindered by a lack of detailed sedimentary records from which to evaluate cause and effect. Here, we link Middle Jurassic environmental, climatic, and floral changes with volcanism using records from the Dameigou section of the Qaidam Basin on the Qinghai-Tibet Plateau. High-resolution chemostratigraphic (δ13Corg patterns) and biostratigraphic (palynological fossils) data reveal three negative organic carbon isotope excursions (NCIE) at the Aalenian-Bajocian boundary, the Bajocian-Bathonian boundary, and in the middle of the Callovian, respectively. The first two NCIEs (NCIE-I and NCIE-II) were accompanied by relatively warm and humid climatic conditions and coal accumulation. In contrast, the third NCIE (NCIE-III) was accompanied by warm but dry climatic conditions, a decrease in coal accumulation, a decline in plant diversity, the significant decline in fern spore diversity and abundance, and a rapid increase in the abundance of Classopollis pollen (based on petrological, palynological, PCA, Hydrophyte/Xerophyte ratio, and nMDS data). Four sedimentary mercury anomalies (Hg/Al spikes) have temporal coincidence with the three NCIEs and climate warming events, suggesting a volcanic origin for these. We suggest that volcanism was a key driver of Middle Jurassic change, with major pulses releasing large amounts of CO2 and Hg into the atmosphere, resulting in Hg loading, NCIEs, climatic warming, and floral changes in terrestrial strata. Our multi-proxy study provides new insights into the links between volcanism and terrestrial environmental, climatic, and floral changes during the Middle Jurassic

Optimal Route Design for Construction Waste Transportation Systems: Mathematical Models and Solution Algorithms

A huge amount of construction waste is generated in construction sites every day that needs to be transported by vehicle to disposal facilities for processing. Unlike in most typical transportation problems, once these vehicles are loaded with construction waste, they must travel directly to the disposal facility. Moreover, there are different types of construction waste that may require handling by different disposal facilities. In this paper, we develop a model and algorithm for identifying the optimal transportation routes specific to construction waste transportation. Our results can not only minimize the overall costs for both the logistics company and the contractor but also minimize the distance traveled, thus reducing urban traffic emissions

Primary care team and its association with quality of care for people with multimorbidity: a systematic review

Abstract Background Multimorbidity is posing an enormous burden to health systems, especially for primary healthcare system. While primary care teams (PCTs) are believed to have potentials to improve quality of primary health care (PHC), less is known about their impact on the quality of care for people with multimorbidity. We assessed the characteristics of PCTs and their impact on the quality of care for people with multimorbidity and the mechanisms.  Methods We searched PubMed, MEDLINE, EMBASE, ProQuest for published studies from January 2000 to October 2021 for studies in English. Following through PRISMA guidelines, two reviewers independently abstracted data and reconciled by consensus with a third reviewer. Titles, abstracts, and full texts were evaluated to identify relevant studies. Studies were categorized by types of interventions, the impact of interventions on outcome measures, and mechanisms of interventions.  Results Seventeen studies (13 RCT, 3 cohort studies, and 1 non-randomized trial) were identified. PCTs were summarized into three types—upward PCTs, downward PCTs and traditional PCTs according to the skill mix. The upward PCTs included primary care workers and specialists from upper-level hospitals, downward PCTs involving primary care workers and lay health workers, and traditional PCTs involving physicians and care managers. PCTs improved patients’ mental and psychological health outcomes greatly, and also improved patients’ perceptions towards care including satisfaction with care, sense of improvement, and patient-centeredness. PCTs also improved the process of care and changed providers’ behaviors. However, PCTs showed mixed effects on clinical outcome measures. Conclusions PCTs have improved mental and psychological health outcomes, the process of care, patients’ care experiences, and satisfaction towards care for patients with multimorbidity. The effect of PCTs on clinical outcomes and changes in patient behaviors need to be further explored

A new strategy to pretreat carbon nanofiber and its application in determination of dopamine

A novel sonochemical process, using hydrogen peroxide in a laboratory ultrasonic bath, was employed to pretreat the carbon nanofiber (CNF) for creating oxygen-rich groups on the surface of CNF. After the sonochemical process, the CNF showed good hydrophilicity and high electrochemical activity. Compared to normal pretreatment process, this sonochemical process is timesaving and effective for dispersion and functionalization of CNF. The resulting CNF showed high catalytic activity toward the oxidation of DA. A carbon paste electrode modified by CNF (CPE-CNF) was used to determine the dopamine (DA) in the presence of ascorbic acid (AA). The detection limit is 0.05 μM, with the linear range from 0.05 μM to 6.4μM

A New Strategy to Pretreat Carbon Nanofiber and Its Application in Determination of Dopamine

A novel sonochemical process, using hydrogen peroxide in a laboratory ultrasonic bath, was employed to pretreat the carbon nanofiber (CNF) for creating oxygen-rich groups on the surface of CNF. After the sonochemical process, the CNF showed good hydrophilicity and high electrochemical activity. Compared to normal pretreatment process, this sonochemical process is timesaving and effective for dispersion and functionalization of CNF. The resulting CNF showed high catalytic activity toward the oxidation of DA. A carbon paste electrode modified by CNF (CPE-CNF) was used to determine the dopamine (DA) in the presence of ascorbic acid (AA). The detection limit is 0.05 μM, with the linear range from 0.05 μM to 6.4 μM

Optimal Ship Deployment and Sailing Speed under Alternative Fuels

The European Union (EU) has implemented a sub-quota of 2% for renewable marine fuels to be utilized by vessels operating within its jurisdiction, effective starting from 2034. This progressive policy signifies a significant leap towards reducing carbon emissions and promoting sustainable development. However, it also presents notable challenges for shipping companies, particularly in terms of fuel costs. In order to support shipping companies in devising optimal strategies within the framework of this new policy, this study proposes a mixed-integer linear programming model. This model aims to determine the optimal decisions for fuel choice, sailing speed and the number of vessels on various routes. Furthermore, we showcase the adaptability of our model in response to fluctuations in fuel prices, relevant vessel costs, and the total fleet size of vessels. Through its innovative insights, this research provides invaluable guidance for optimal decision-making processes within shipping companies operating under the new EU policy, enabling them to minimize their total costs effectively

Fault Geometry and Mechanism of the Mw 5.7 Nakchu Earthquake in Tibet Inferred from InSAR Observations and Stress Measurements

Different types of focal mechanism solutions for the 19 March 2021 Mw 5.7 Nakchu earthquake, Tibet, limit our understanding of this earthquake’s seismogenic mechanism and geodynamic process. In this study, the coseismic deformation field was determined and the geometric parameters of the seismogenic fault were inverted via Interferometric Synthetic Aperture Radar (InSAR) processing of Sentinel-1 data. The inversion results show that the focal mechanism solutions of the Nakchu earthquake are 237°/69°/−70° (strike/dip/rake), indicating that the seismogenic fault is a NEE-trending, NW-dipping fault dominated by the normal faulting with minor sinistral strike-slip components. The regional tectonic stress field derived from the in-situ stress measurements shows that the orientation of maximum principal compressive stress around the epicenter of the Nakchu earthquake is NNE, subparallel to the fault strike, which controlled the dominant normal faulting. The occurrence of seven M ≥ 7.0 historical earthquakes since the M 7.0 Shenza earthquake in 1934 caused a stress increase of 1.16 × 105 Pa at the hypocenter, which significantly advanced the occurrence of the Nakchu earthquake. Based on a comprehensive analysis of stress fields and focal mechanisms of the Nakchu earthquake, we propose that the dominated normal faulting occurs to accommodate the NE-trending compression of the Indian Plate to the Eurasian Plate and the strong historical earthquakes hastened the process. These results provide a theoretical basis for understanding the geometry and mechanics of the seismogenic fault that produced the Nakchu earthquake