Prediction and Design of Protease Enzyme Specificity Using a Structure-Aware Graph Convolutional Network.

Site-specific proteolysis by the enzymatic cleavage of small linear sequence motifs is a key post-translational modification involved in physiology and disease. The ability to robustly and rapidly predict protease substrate specificity would also enable targeted proteolytic cleavage - editing - of a target protein by designed proteases. Current methods for predicting protease specificity are limited to sequence pattern recognition in experimentally-derived cleavage data obtained for libraries of potential substrates and generated separately for each protease variant.

Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection.

RNA therapy represents a great way to precisely regulate cellular processes by modulating the gene expression. Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self-regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed.

Giant Exchange-Bias-Like Effect at Low Cooling Fields Induced by Pinned Magnetic Domains in Y NiIrO Double Perovskite.

Exchange bias (EB) is highly desirable for widespread technologies. Generally, conventional exchange-bias heterojunctions require excessively large cooling fields for sufficient bias fields, which are generated by pinned spins at the interface of ferromagnetic and antiferromagnetic layers. It is crucial for applicability to obtain considerable exchange-bias fields with minimum cooling fields.

Incorporation of an Isohexide Subunit Improves the Drug-like Properties of Bioactive Compounds.

An enhanced ability to pre-engineer favorable drug-likeness qualities into bioactive molecules would focus and streamline the drug development process. We find that phenols, carboxylic acids, and a purine react with isosorbide ("GRAS" designated) under Mitsunobu coupling conditions to deliver the isoidide conjugates selectively and efficiently. Such conjugates show improved solubility and permeability properties compared with the bare scaffold compounds themselves, and the purine adduct may have applications as a 2'-deoxyadenosine isostere.

Syntactic bootstrapping with clausal complements of adjectives.

Like verbs, adjectives pose a challenge to the young word learner in that some - like or - map onto properties that are detectable through the senses, while others - like - express abstract properties that have no reliable, physical correlate. Even for those adjectives whose properties are observable, how does a child know that one particular property is being highlighted above all others? The physical environment alone will not suffice. Just as with verbs, the child learning adjectives is faced with an inherent indeterminacy of meaning, which can only be resolved through the incorporation of cues originating from multiple sources.

Four principles to establish a universal virus taxonomy.

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus.

Effect of Pre-Storage CO Treatment and Modified Atmosphere Packaging on Sweet Pepper Chilling Injury.

The effect of 10% CO pre-storage treatment for 12, 24, and 48 h alongside modified atmosphere packaging (MAP) on chilling injury was determined in this study. This study found significant interactions between chilling injuries and cell membrane damage indicators. The results show that chilling injuries can be somewhat reduced by the use of CO treatment for sweet peppers.

Reliability and validity of a Global Physical Activity Questionnaire adapted for use among pregnant women in Nepal.

Background: Physical activity (PA) plays an important role in optimizing health outcomes throughout pregnancy. In many low-income countries, including Nepal, data on the associations between PA and pregnancy outcomes are scarce, likely due to the lack of validated questionnaires for assessing PA in this population. Here we aimed to evaluate the reliability and validity of an adapted version of Global Physical Activity Questionnaire (GPAQ) among a sample of pregnant women in Nepal.

The dynamics of the microbiome in Ixodidae are shaped by tick ontogeny and pathogens in Sarawak, Malaysian Borneo.

Tick-borne diseases have recently been considered a potential emerging public health threat in Malaysia; however, fundamental studies into tick-borne pathogens and microbiome appear limited. In this study, six tick species (, , and ) collected from two primary forests and an oil palm plantation in Sarawak, Malaysian Borneo, were used for microbiome analysis targeting bacterial 16S rDNA using next-generation sequencing (NGS). In addition, bacterial species were further characterized in conventional PCRs to identify potential pathogens.

The Association of Psychiatric Comorbidities With Short-Term and Long-Term Outcomes Following Spinal Cord Stimulator Placement.

Background: Outcomes after spinal cord stimulator (SCS) placement are affected by psychologic comorbidities. It is part of routine practice to do psychologic assessments prior to SCS trials to assess for the presence of maladaptive behavioral patterns. However, few studies have sought to quantify the effect of psychiatric comorbidities on complications, reoperation, and readmission rates.

Recent Advances in Biologic Therapeutic N-Glycan Preparation Techniques and Analytical Methods for Facilitating Biomanufacturing Automation.

N-glycosylation is a post-translational modification that occurs during the production of monoclonal antibody (mAb) therapeutics. During production of mAb based therapeutics the use of various hosts and cell culture additives attribute to glycan heterogeneity. The safety and efficacy of monoclonal antibodies with mechanism of actions that utilize Fc effector functions can be negatively impacted by glycan heterogeneity and thus is often considered a critical quality attribute (CQA).

Effect of Penetration Enhancers on Transdermal Delivery of Oxcarbazepine, an Antiepileptic Drug Using Microemulsions.

Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the transdermal delivery of OXC from microemulsions using different penetration enhancers. Transcutol® P (TRC), oleic acid (OA), cineole (cin), Labrasol (LS), Tween 80 (T80) and N-Methyl-Pyrrolidone (NMP) were used as penetration enhancers as well as microemulsion components.

Implementation and scaling-up of an effective mHealth intervention to increase adherence to triage of HPV-positive women (ATICA study): perceptions of health decision-makers and health-care providers.

Background: The ATICA study was a Hybrid I type randomized effectiveness-implementation trial that demonstrated effectiveness of a multicomponent mHealth intervention (Up to four SMS messages sent to HPV-positive women, and one SMS message to CHWs to prompt a visit of women with no triage Pap 60 days after a positive-test), to increase adherence to triage of HPV positive women (ATICA Study). We report data on perceptions of health decision-makers and health-care providers regarding the intervention implementation and scaling-up.

Methods: A qualitative study was carried out based on individual, semi-structured interviews with health decision-makers (n = 10) and health-care providers (n = 10).

Standardized protocol for the evaluation of chimeric antigen receptor (CAR)-modified cell immunological synapse quality using the glass-supported planar lipid bilayer.

Chimeric antigen receptor (CAR)-modified cell therapy is an effective therapy that harnesses the power of the human immune system by re-engineering immune cells that specifically kill tumor cells with tumor antigen specificity. Key to the effective elimination of tumor cells is the establishment of the immunological synapse (IS) between CAR-modified immune cells and their susceptible tumors. For functional activity, CAR-modified cells must form an effective IS to kill tumor cells specifically.

Evaluation of eGFP expression in the ChAT-eGFP transgenic mouse brain.

Background: A historically definitive marker for cholinergic neurons is choline acetyltransferase (ChAT), a synthesizing enzyme for acetylcholine, (ACh), which can be found in high concentrations in cholinergic neurons, both in the central and peripheral nervous systems. ChAT, is produced in the body of the neuron, transported to the nerve terminal (where its concentration is highest), and catalyzes the transfer of an acetyl group from the coenzyme acetyl-CoA to choline, yielding ACh. The creation of bacterial artificial chromosome (BAC) transgenic mice that express promoter-specific fluorescent reporter proteins (green fluorescent protein-[GFP]) provided an enormous advantage for neuroscience.

Exposure to a Youth-Led Sexual Violence Prevention Program Among Adolescents: The Impact of Engagement.

Objective: Most studies of peer sexual violence (SV) prevention programs for adolescents focus on program outcomes or feasibility and acceptability; few examine how exposure levels or dosage affects impact. The present study examined the effects of attending multiple community-located youth-led prevention events, as compared to attending one or none, on peer violence (PV)-related attitudes and behaviors.

Method: Middle and high school students ( at first wave = 13.

The Quebec Cannabis Registry: Investigating the Safety and Effectiveness of Medical Cannabis.

To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment.

The two sRNAs OmrA and OmrB indirectly repress transcription from the LEE1 promoter of enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic bacterium that predominantly infects infants in developing countries. EPEC forms attaching and effacing (A/E) lesions on the apical surface of the small intestine, leading to diarrhea. The locus of enterocyte effacement (LEE) is both necessary and sufficient for A/E lesion morphogenesis by EPEC.

The Antinarcolepsy Drug Modafinil Reverses Hypoglycemia Unawareness and Normalizes Glucose Sensing of Orexin Neurons in Male Mice.

Perifornical hypothalamus (PFH) orexin glucose-inhibited (GI) neurons that facilitate arousal have been implicated in hypoglycemia awareness. Mice lacking orexin exhibit narcolepsy, and orexin mediates the effect of the antinarcolepsy drug modafinil. Thus, hypoglycemia awareness may require a certain level of arousal for awareness of the sympathetic symptoms of hypoglycemia (e.