Centuries of human development have altered the connectivity of rivers, adversely impacting ecosystems and the services provided. Significant investments in natural resource projects are made annually with the goal to restore function to degraded rivers and floodplains and protect freshwater resources. Yet restoration projects often fall short of their objectives, in part, due to the lack of systems-based, strategic planning. To evaluate channel-floodplain (dis)connectivity and erosion/incision hazard at the regional scale, we calculate Specific Stream Power (SSP), an estimate of the energy of a river, using a topographically-based, low-complexity hydraulic model. Other basin-wide SSP modeling approaches neglect reach-specific geometric information embedded in Digital Elevation Models. Our approach leverages this information to generate reach-specific SSP-flow curves. We extract measures from these curves that describe (dis)connected floodwater storage capacity and erosion hazard at individual design storm flood stages and demonstrate how these measures may be used to identify watershed-scale patterns in connectivity. We show proof-of-concept using 25 reaches in the Mad River watershed in central Vermont and demonstrate that the SSP results have acceptable agreement with a well-calibrated process-based model (2D Hydraulic Engineering Center’s River Analysis System) across a broad range of design events. While systems-based planning of regional restoration and conservation activities has been limited largely due to computational and human resource requirements, measures derived from low complexity models can provide an overview of reach-scale conditions at the regional level and aid planners in identifying areas for further restoration and/or conservation assessments.

Background We estimated the secondary attack rate of SARS-CoV-2 among household contacts of PCR-confirmed cases of COVID-19 in rural Kenya and analysed risk factors for transmission. Methods We enrolled incident PCR-confirmed cases and their household members. At baseline, a questionnaire, a blood sample, and naso-oropharyngeal swabs were collected. Household members were followed 4, 7, 10, 14, 21 and 28 days after the date of the first PCR-positive in the household; naso-oropharyngeal swabs were collected at each visit and used to define secondary cases. Blood samples were collected every 1-2 weeks. Symptoms were collected in a daily symptom diary. We used binomial regression to estimate secondary attack rates and survival analysis to analyze risk factors for transmission. Results A total of 119 households with at least one positive household member were enrolled between October 2020 and September 2022, comprising 503 household members; 226 remained in follow up at day-14 (45%). A total of 43 secondary cases arose within 14 days of identification of the primary case, 81 household members remained negative. The 7-day secondary attack rate was 4% (95%CI 1-10%), the 14-day secondary attack rate was 28% (95%CI 17-40%). Of 38 secondary cases with data, 8 reported symptoms (21%, 95%CI 8-34%). Antibody to SARS-CoV-2 spike protein at enrolment was not associated with risk of becoming a secondary case. Conclusion Households in our setting experienced a lower 7-day attack rate than a recent meta-analysis indicated as the global average (23-43% depending on variant), and infection is mostly asymptomatic in our setting.

Background and Purpose: Peripheral nerve trauma-induced dysregulation of pain-associated genes in the primary sensory neurons of dorsal root ganglion (DRG) contributes to neuropathic pain genesis. RNA-binding proteins participate in gene transcription. We hypothesized that RALY, an RNA-binding protein, participated in nerve trauma-induced dysregulation of DRG pain-associated genes and nociceptive hypersensitivity. Methods and results: Immunohistochemistry staining showed that RALY was expressed exclusively in the nuclei of DRG neurons. Peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve produced time-dependent increases in the levels of Raly mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno-associated virus 5 (AAV5)-expressing Raly shRNA reduced the CCI-induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (eIF4G2) mRNA and eIF4G2 protein in injured DRG and mitigated the development and maintenance of CCI-induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing Raly mRNA upregulated the expression of eIF4G2 mRNA and eIF4G2 protein in the DRG and led to hypersensitive responses to noxious stimuli in the absence of nerve trauma. Mechanistically, CCI promoted the binding of RALY to the promoter of eIF4G2 gene and triggered its transcriptional activity. Conclusion and Implications: Our findings indicate that RALY participates in nerve trauma-induced nociceptive hypersensitivity likely through transcriptionally triggering eIF4G2 expression in the DRG. RALY may be a potential target in neuropathic pain management.

Background and Purpose Development of core concepts in disciplines such as biochemistry, microbiology, and physiology transformed teaching. They provided the foundation for the development of teaching resources for global educators, as well as valid and reliable approaches to assessment. An international research consensus recently identified 25 core concepts of pharmacology. The current study aimed to define and unpack these concepts. Experimental approach A two-phase, iterative approach, involving 60 international pharmacology education experts was used. The first phase involved drafting definitions for the core concepts and identifying key sub-concepts via a series of online meetings and asynchronous work. These were refined in the second phase, through a two-day hybrid workshop followed by a further series of online meetings and asynchronous work. Key Results The project produced consensus definitions for a final list of 24 core concepts and 103 sub-concepts of pharmacology. The iterative, discursive methodology resulted in the modification concepts from the original study, including the change of ‘drug-receptor interaction’ to ‘drug-target interaction’ and the change of the core concept ‘agonists and antagonists’ to sub-concepts of drug-target interaction. Conclusion and Implications The definitions and sub-concepts of the 24 core concepts provide an evidence-based foundation for pharmacology curricula development and evaluation. The next steps for this project include the development of a concept inventory to assess acquisition of the concepts, as well as the development of cases studies and educational resources to support teaching by the global pharmacology community, and student learning of the most critical and fundamental concepts of the discipline.

Medical progress as enabled by early plasma products has also revealed biological safety challenges. The combination of donor selection, donation testing and virus reduction processes has effectively addressed these concerns, and today medicinal plasma products feature significant safety margins. The safety tripod concept has since been adapted to biotechnology manufacturing platforms and has also ensured the safety of these products. However, cell-based manufacturing processes have occasionally been exposed to adventitious viruses, leading to manufacturing interruptions and unstable supply situations. The rapid progress of advanced therapy medicinal products (ATMPs) needs an innovative approach to ensure the learnings from more traditional biotechnology help to avoid any unwelcome reminder of the universal presence of viruses. The introduction of up-stream virus clearance steps has already been shown to be valuable for any products too complex for down-stream interventions in the sense of both assuring product safety and continuous supply. The gentlest method being virus filtration – the development of which is presented here. The experiments investigated the feasibility of implementing culture media virus filtration with respect to their virus clearance capacities under extreme conditions such as very high process feed loading (up to ~ 19,000 L/m 2), very long duration (up to 31 days), and multiple process interruptions (up to 21, with cumulative interruptions of over 92 hours). Minute virus of mice (MMV) was used as a relevant target virus, and in general, as a model small non-enveloped virus, as these viruses are the main challenge for the investigated virus filters with a stipulated pore-size of about 20 nm. It was found that certain filters – especially of the newer 2 nd generation – are capable of effective virus clearance despite the harsh regimen they were subjected to. At the same time the investigation of biochemical parameters for un-spiked control runs showed the filters to have no measurable impact on the composition of the culture media. Based on these findings, this technology seems to be quite feasible for large volume pre-manufacturing process culture media preparations.

Investigating the response characteristics of various hydrological factors to the construction of water conservancy projects and evaluating their impact on the ecological environment is crucial for ecological protection and restoration in the Loess Plateau, China with a complex environment. In this study, we employed a geomorphology-based hydrological model to simulate the hydrological elements of the Qinhe River Basin in the Loess Plateau. Additionally, we explored the response characteristics of the water cycle and hydrological processes to the construction of reservoirs in the basin. We also examined multiyear changes in peak flood volume and sediment discharge during flood seasons influenced by reservoirs. A thorough evaluation of the simulation results indicated their reliability. The sub-basins hosting reservoirs initially showed an increase in evaporation, followed by a decrease. During the change periods, both runoff and soil water decreased, but remained higher than the mean values for the basin during the same period. The Normalized Difference Vegetation Index of sub-basins associated with five reservoirs was significantly higher than the mean value for the basin during the same period. The peak flood volume and sediment discharge in the basin were characterized by decreasing trends, with the latter showing weak sustainability. The value of each index for a sub-basin associated with a reservoir was higher than the average value for the basin. The construction and operation of reservoirs had a positive impact on the ecology of the basin. Water and soil conservation measures, including sediment regulation and storage using reservoirs, significantly decreased water-related disasters and soil erosion in the basin. This study provides a scientific basis for the design of water conservancy projects and ecological governance in the basin.

The electrochemical performance of Polyaniline (PANI) can be significantly improved due to the incorporation of spinel-type transition metal oxide, i.e., 1 wt. % of Nickel Ferrite (NiFe 2O 4) into the PANI matrix. In this report, we have synthesised NiFe 2O 4 (NF), PANI1:1 ratio, PANI1:2 ratio, and PANI/NiFe 2O 4 nanocomposites, i.e., PANI1:1/NF1 and PANI1:2/NF2 nanocomposites by in-situ oxidative polymerization method. The conducting network formed in the nanocomposite significantly increases the multiple valence states of the metal for the electrolytic ions. The PANI/NiFe 2O 4 nanocomposite shows good interaction and was confirmed by Fourier Transform Infra-red Spectroscopy (FTIR) and Raman analysis. The SEM analysis reveals a uniformly porous and agglomerated globular morphology of the nanocomposite. Also, the PANI/NiFe 2O 4 composite (PANI1:1/NF1) exhibits enhanced supercapacitive properties due to improve strong conducting path of PANI, which helps to provide the delocalization of the electrons in the polymeric chain. The highest specific capacitance ~ 758 Fg -1 is achieved for PANI 1:1/NF1 sample as compared to bare PANI1:1 (677 Fg -1), PANI1:2 (500 Fg -1), NF (253 Fg -1) and other PANI1:2/NF2 (686 Fg -1) samples at 10 mV/s scan rate in a two-electrode system due to NF nanoparticles filling the vacant places in the polymeric matrix. The energy density (54 Whkg -1), power density (1705 Wkg -1) and good cycling stability approx. 97 % after 10000 GCD cycles of the device is found for PANI1:1/NF1. The EIS studies further confirm that the PANI 1:1/NF1 device has a lower charge transfer resistance (R ct) ~ 0.35 Ohm in comparison to other fabricated devices. It seems that NiFe 2O 4 acts as a “superhighway” for charge transportation between PANI which is beneficial for supercapacitors.

Acquisition of new genes often results in the emergence of novel functions and is a key step in lineage-specific adaptation. As the only group of sessile crustaceans, barnacles establish permanent attachment through initial cement secretion at the larval phase followed by continuous cement secretion in juveniles and adults. However, the origins and evolution of barnacle larval and adult cement proteins remain poorly understood. By performing microdissection of larval cement glands, transcriptome and shotgun proteomics and immunohistochemistry validation, we identified 30 larval and 27 adult cement proteins of the epibiotic turtle barnacle Chelonibia testudinaria, of which the majority are stage- and barnacle-specific. While only two proteins, SIPC and CP100K, were expressed in both larvae and adults, detection of protease inhibitors and the cross-linking enzyme lysyl oxidase paralogs in larvae and adult cement suggested functional convergence. Other barnacle specific cement proteins such as CP100k and CP52k likely share a common origin dating back at least to the divergent of Rhizocephala and Thoracica. Different CP52k paralogs could be detected in larval and adult cement, suggesting stage-specific cement proteins may arise from duplication followed by changes in expression timing of the duplicates. Interestingly, the biochemical properties of larval- and adult-specific CP52k paralogs exhibited remarkable differences, reflecting the composition of cement in different life stages of turtle barnacle might be chemically different. We conclude that de novo gene formation and duplicate neofunctionalization are pivotal to the evolution of lineage-specific cement toolkits in barnacles, which may explain how barnacles can inhabit diverse marine substrata.

Sperm morphology is considered a species-specific character and has been used as a tool in the classification of numerous mammalian taxa. Neotropical bats have been poorly studied, and important aspects on sperm morphology have not been elucidated. The aim of the present study was to describe and compare the sperm morphology and morphometry of Molossus molossus and Molossops temminckii. 14 adults specimens were analyzed from the Colección Mamíferos Lillo, Universidad Nacional de Tucumán: five Molossus molossus and nine Molossops temminckii. The epididymis were extracted and macerated in Farmer’s solution, followed by a coloration with different stains. To carry out the description and morphometric analysis, microphotographs were taken under an optical, epifluorescence and scanning electron microscope. A total of 50 sperm from each individual were measured for morphometric analysis. The length and width of the head, midpiece and tail were taken as variables. Sperm from M. molossus and M. temminckii were practically identical, both morphologically and morphometrically. In both species, a distal bulge was observed at the end of the intermediate piece in a percentage greater than 85%. The main characteristics shared between the species were: presence of acrosomal blebs in the upper half of the head of the spermatozoa; cephalic equatorial segment with filiform ornamentations; intermembrane space of head apex wedge-shaped; helical middle piece and annulus at the end of middle piece. In the present study, scanning electron microscopy allowed us to visualize structures, such as acrosomal vesicles, that were not detected with other types of microscopy.

Comprehensive treatment for ROS1-overexpressed pulmonary sarcomatoid carcinoma: a case report

PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia ( Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for tick acquisition; however, the biological function of PlzA has remained enigmatic. Here we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.

Preventive algorithm ending up being the ‘Cause’!Anindya Ghosh, MD1 │ Deep Chandh Raja, MD21Department of Cardiac Electrophysiology and Pacing, Arrhythmia Heart Failure Academy, The Madras Medical Mission, Chennai, Tamil Nadu, India2Department of Cardiac Electrophysiology and Pacing, Kauvery Hospital, Chennai, India

Aim: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with hematologic malignancy, identify factors affecting methotrexate PK, and propose optimal dosage regimen for the Korean population. Methods: Data were retrospectively collected from 188 patients with acute leukemia or non-Hodgkin’s lymphoma who were admitted to Severance Hospital for the period from 2005 to 2015. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model. Results: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.99L for central volume of distribution (V_1), 18.76L for peripheral volume of distribution (V_2), 12.9L/h for clearance (CL) and 0.646L/h for inter-compartmental clearance. Covariate analyses showed that, at the weight of 50kg, CL decreased by 0.11 L/h for each one-year increase in age above 14 years old and decreased to 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (=V_1+V_2) was 0.90L/kg, which was similar to those in the Western or Chinese population. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen. Conclusion: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with hematologic malignancy.

Ultra-narrow bandgap (ultra-NBG) small molecule acceptors (SMAs) show great potential in organic solar cells (OSCs) due to the extend-ed near-infrared (NIR) absorption. In this work, a synergetic alkoxy side-chain and chlorine-contained end group strategy is employed to achieve A-DA’D-A type ultra-NBG SMAs by introducing alkoxy chains with oxygen atom at the second position into the thiophene β posi-tion as well as replacing the F atoms with Cl atoms in the end group. As a result, the heptacyclic BZO-4F shows a redshifted absorption onset (960 nm) than Y11 (932 nm) without oxygen atoms in the side chains. Then, the fluorinated end groups are substituted with the chlorinated ones to synthesize BZO-4Cl. The absorption onset of BZO-4Cl is further redshifted to 990 nm, corresponding to an optical ultra-NBG of 1.25 eV. When blending with the polymer donor PBDB-T, the binary devices based on PBDB-T: BZO-4F and PBDB-T: BZO-4Cl delivers power conversion efficiencies (PCEs) over 12%. Furthermore, ternary devices with the addition of BZ4F-O-1 into PBDB-T: BZO-4Cl system achieve the optimal PCE of 15.51%. This work proposes a synergetic alkoxy side-chain and chlorine-contained end group strategy to achieve A-DA’D-A type ultra-NBG SMAs, which is important for future molecular design.

Mini-Commentary on BJOG-22-0480.R1:‘Perinatal outcomes of socially disadvantaged women in Australia: A population-based retrospective cohort study ’

Vector-borne diseases cause significant financial and human loss, with billions of dollars spent on control. Arthropod vectors experience a complex suite of environmental factors that affect fitness, population growth, and species interactions across multiple spatial and temporal scales. Temperature and water availability are two of the most important abiotic variables influencing their distributions and abundances. While extensive research on temperature exists, the influence of humidity on vector and pathogen parameters affecting disease dynamics are less understood. Humidity is often underemphasized, and when considered, is often treated as independent of temperature even though desiccation likely contributes to declines in trait performance at warmer temperatures. This Perspectives explores how humidity shapes the thermal performance of mosquito-borne pathogen transmission. We summarize what is known about its effects and propose a conceptual model for how temperature and humidity interact to shape the range of temperatures across which mosquitoes persist and achieve high transmission potential. We discuss how failing to account for these interactions hinders efforts to forecast transmission dynamics and respond to epidemics of mosquito-borne infections. We outline future research areas that will ground the effects of humidity on the thermal biology of pathogen transmission in a theoretical and empirical framework to improve spatial and temporal prediction of vector-borne pathogen transmission.

In CASP15 there was a greater emphasis on multimeric modelling than in previous experiments, with assembly structures nearly doubling in number (41 up from 22) since the previous round. CASP15 also included a new estimation of model accuracy (EMA) category in recognition of the importance of objective quality assessment for quaternary structure models. ModFOLDdock is a multimeric model quality assessment server developed by the McGuffin group at the University of Reading, which brings together a range of single-model, clustering and deep learning methods to form a consensus of approaches. For CASP15 three variants of ModFOLDdock were developed to optimise for the different facets of the quality estimation problem. The standard ModFOLDdock variant produced predicted scores optimised for positive linear correlations with the observed scores. The ModFOLDdockR variant produced predicted scores optimised for ranking, i.e., the top-ranked models have highest accuracy. In addition, the ModFOLDdockS variant used a quasi-single model approach to score each model on an individual basis. The scores from all three variants achieved strongly positive Pearson correlation coefficients with the CASP observed scores (oligo-lDDT) in excess of 0.70, which were maintained across both homomeric and heteromeric model populations. In addition, at least one of the ModFOLDdock variants was consistently ranked in the top two methods across all three EMA categories. Specifically, for overall global fold prediction accuracy, ModFOLDdock placed second and ModFOLDdockR placed third; for overall interface quality prediction accuracy ModFOLDdockR, ModFOLDdock and ModFOLDdockS were placed above all other predictor methods, and ModFOLDdockR and ModFOLDdockS were placed second and third respectively for individual residue confidence scores. The ModFOLDdock server is available at: [https://www.reading.ac.uk/bioinf/ModFOLDdock/](https://www.reading.ac.uk/bioinf/ModFOLDdock/). ModFOLDdock is also available as part of the MultiFOLD docker package: [https://hub.docker.com/r/mcguffin/multifold](https://hub.docker.com/r/mcguffin/multifold)

Proteins play an essential role in the vital biological processes governing cellular functions. Most proteins function as members of macromolecular machines, with the network of interacting proteins revealing the molecular mechanisms driving the formation of these complexes. Profiling the physiology-driven remodeling of these interactions within different contexts constitutes a crucial component to achieving a comprehensive systems-level understanding of interactome dynamics. Here, we apply co-fractionation mass spectrometry and computational modeling to quantify and profile the interactions of ~2,000 proteins in the bacterium Escherichia coli cultured under ten distinct culture conditions. The resulting quantitative co-elution patterns revealed large-scale condition-dependent interaction remodeling among protein complexes involved in diverse biochemical pathways in response to the unique environmental challenges. Network-level analysis highlighted interactome-wide biophysical properties and structural patterns governing interaction remodeling. Our results provide evidence of the local and global plasticity of the E. coli interactome along with a rigorous generalizable framework to define protein interaction specificity. We provide an accompanying interactive web application to facilitate exploration of these rewired networks.