Leptospirosis is a significant zoonosis worldwide, with disease severity ranging from a mild non-specific illness to multi-organ dysfunction and hemorrhage. The disease is caused by pathogenic bacteria of the genus Leptospira, which are classified into pathogenic and saprophytic clades. Bacterial binding to host molecules and cells, coordinated by adhesin proteins, is an important step in pathogenesis. While many leptospiral adhesins have been identified, the vast majority have not been characterized in vivo. Herein, we present an overview of the current methodologies and successes in identifying adhesins in Leptospira, including known biological roles in vivo. We will also identify and discuss potential areas for future research.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. As MNTs are composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module appears advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated a high affinity for target receptors, as revealed by fluorescent-labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNTs. Thus, this work reveals that MNT\'s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

Selectively remembering more valuable information can improve memory efficiency. Such value effects have been observed on long-term memory for item-colour binding, but the possible contributory factors are unclear. The current study explored contributions from attention (Experiment 1) and verbal rehearsal (Experiment 2). Across two experiments, memory was superior for item-colour bindings that were associated with high (relative to low) point values at encoding, both in an immediate test and a delayed re-test. When availability of attentional resources was reduced during encoding, value only influenced immediate and not delayed memory (Experiment 1). This indicates that a transient value effect can be obtained with little attentional resources, but attentional resources are involved in creating a longer lasting effect. When articulatory suppression was implemented during encoding (Experiment 2), value effects were somewhat reduced in the immediate test and abolished in the delayed re-test, suggesting a role for verbal rehearsal in value effects on item-colour binding memory. These patterns of value effects did not interact with encoding presentation format (i.e., sequential vs. simultaneous presentation of objects). Together, these results suggest that attentional resources and verbal rehearsal both contribute to value effects on item-colour binding memory, with varying impacts on the durability of these effects.

Feature binding is the process of integrating features, such as colour and shape, into object representations. A persistent question in the literature concerning whether feature binding is an automatic or resource-demanding process may depend on unitisation, that is, whether the to-be-bound information is intrinsic (belonging to) or extrinsic (contextual). Given extensive evidence showing that Easterners may process information more holistically than Westerners, such cultural differences may be useful to understand the fundamental processes of feature binding in visual working memory (WM). Accordingly, we recruited British and Chinese participants to complete a visual WM task wherein to-be-remembered colours were integrated within (i.e., intrinsic binding) or as backgrounds (i.e., extrinsic binding) of to-be-remembered shapes (Experiments 1 and 2). Experiment 2 further investigated the role of prior knowledge in long-term memory to facilitate feature binding in WM. During retrieval, participants decided among three probes: a target, a lure (i.e., recombination of the presented features), and a new colour/shape. Hierarchical Bayesian multinomial processing tree models were fit to the data to estimate parameters representing binding and item memory. The current results suggest that intrinsic and extrinsic binding memory are similar between the two cultural groups, with no prior knowledge benefits for either intrinsic or extrinsic binding for either cultural group. This result conflicts with the Analytic and Holistic framework and suggests that there are no cultural differences or prior knowledge benefits in feature binding.

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that is frequently modified by glycosylation post-translationally. In cancer, EGFR amplifications and hotspot mutations such as L858R that promote proliferation have been detected in a significant fraction of non-small cell lung carcinomas and breast adenocarcinomas. Molecular dynamic simulations suggested that glycosylation at asparagine residue 361 (N361) promotes dimerization and ligand binding. We stably expressed glycosylation-deficient mutant EGFR N361A, with or without the oncogenic mutation L858R. Immunofluorescence and flow cytometry demonstrated that the mutants were each well expressed at the cell membrane. N361A decreased proliferation relative to wild-type EGFR as well as decreased sensitivity to ligands. Proximity ligation assays measuring co-localization of EGFR with its binding partner HER2 in cells revealed that N361A mutations increased co-localization. N361A, located near the binding interface for the EGFR inhibitor necitumumab, desensitized cells expressing the oncogenic EGFR L858R to antibody-based inhibition. These findings underline the critical relevance of post-translational modifications on oncogene function.

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited by infection. Here, we analyze S-directed antibody responses in plasma collected from MERS-CoV-infected individuals. We observe that binding and neutralizing antibodies peak 1-6 weeks after symptom onset/hospitalization, persist for at least 6 months, and neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S1 subunit is immunodominant and that antibodies targeting S1, particularly the receptor-binding domain (RBD), account for most plasma neutralizing activity. Antigenic site mapping reveals that plasma antibodies frequently target RBD epitopes, whereas targeting of S2 subunit epitopes is rare. Our data reveal the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.

OBJECTIVE: Commercial products currently available for sperm selection utilizing hyaluronic acid (HA) binding prior to intracytoplasmic sperm injection (ICSI) are widely used but have some disadvantages. To potentially circumvent these limitations, we compared ICSI using a self-made hyaluronic acid (smHA) reagent with ICSI using SpermSlow.
METHODS: The binding of the reagents to spermatozoa on plastic- or glass-bottom dishes was quantitated using spermatozoa that were isolated by density-gradient centrifugation and swim-up procedures (N = 10/group). Additionally, we investigated the relationship between the HA reagent used prior to ICSI and clinical outcomes after assisted reproduction with HA-ICSI (N = 81).
RESULTS: The smHA reagent exhibited extremely stable binding to human spermatozoa. The binding time of spermatozoa was significantly longer in the smHA reagent than in SpermSlow on both plastic and glass dishes (plastic: 60.0 ± 0.0 min vs. 2.7 ± 5.9 min, P < 0.001; glass: 60.0 ± 0.0 min vs. 2.5 ± 1.8 min, P < 0.001). There were no significant differences in the normal fertilization rate between HA-ICSI with the smHA reagent (128/160, 80.0%) and HA-ICSI with SpermSlow (171/231, 74.0%, P = 0.184). The frequency of the blastocyst development from the HA-ICSI-derived zygote was significantly higher with the smHA reagent (74/101, 73.3%) than with SpermSlow (76/131, 58.0%, P = 0.019). The rates of biochemical pregnancy, clinical pregnancy, fetal heart movement, live birth, and miscarriage were not significantly different between HA-ICSI with the smHA reagent and HA-ICSI with SpermSlow.
CONCLUSIONS: The blastulation rate was higher for HA-ICSI with the smHA reagent as compared with SpermSlow. Clinical outcomes, excluding blastulation, after HA-ICSI were the same using smHA reagent and using SpermSlow. Spermatozoa binding to the smHA reagent was not attenuated over a 60-min time course. In conclusion, this reagent may shorten and simplify HA-ICSI procedures because smHA can be used with any dish material, making it easier to observe the spindle or assess intracytoplasmic morphology.

Understanding how poly(carboxylate)s of chemical admixtures interact with calcium ions in cement pore solutions in the presence of silica fume is fundamental to developing better chemical admixtures for concrete production. In this work, the intermolecular interactions of calcium ions with a poly(carboxylate) superplasticizer type of chemical admixture was investigated via classical all-atom molecular dynamics (MD) simulations and Density Functional Theory (DFT) calculation methods in the presence of silica fume. The classical all-atom MD simulation and DFT calculation results indicate that calcium ions are interacting with oxygen atoms of the carboxylate group of PCE. The better interaction energy could mean an improved adsorption of the PCE segment with calcium ions. In this regard, it can be noted that the ester-based PCE segment could have a better adsorption onto calcium ions in comparison with the ether-based PCE segment. Moreover, the presence of silicon dioxide could improve the adsorption of the PCE segment onto calcium ions.

Lysine is one of the most abundant residues on the surface of proteins and its site-selective functionalization is extremely challenging. The existing methods of functionalization rely on differential reactivities of lysine on a protein, making it impossible to label less reactive lysines selectively. We here report polymeric nanoparticles that mimic enzymes involved in the posttranslational modifications of proteins that distinguish the chemical and supramolecular contexts of a lysine and deliver the labeling reagent precisely to its ε amino group. The nanoparticles are prepared through molecular imprinting of cross-linkable surfactant micelles, plus an in situ, on-micelle derivatization of the peptide template prior to the imprinting. The procedures encode the polymeric nanoparticles with all the supramolecular information needed for sequence identification and precise labeling, allowing single-site functionalization of a predetermined lysine on the target protein in a mixture.

G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin, derived from Curcuma longa, has been known as a quadruplex binder and has a potential role in the apoptosis of cancer cells. Here, we have reported the Schiff base ligand of curcumin synthesized through the condensation of the amino acid L-tryptophan and the knoevenagel derivative of curcumin (4-nitrobenzylidene curcumin (NBC)) as a potential G-quadruplex binder. Thus, spectroscopic and biophysical studies reveal a higher binding affinity of the ligand Sb-NBC towards the promoter and telomere G-quadruplex sequence as compared to the parent NBC. The ligand Sb-NBC highly stabilizes the parallel and hybrid G-quadruplex topologies to 10.5 0C- 6.4 0C. Interestingly, the ligands also exhibit selective cytotoxicity toward cancer cells over normal cells. Taken together, this work provides evidence of the possibility of applying curcumin Schiff base in cancer therapy to regulate oncogene expression in cancer cells.