Selection of DNA aptamers that prevent the fibrillization of α-synuclein protein in cellular and mouse models.

A neuropathological hallmark of Parkinson's disease (PD) is the aggregation and spreading of misfolded α-synuclein (αSyn) protein. In this study, a selection method was developed to identify aptamers that showed affinity for monomeric αSyn and inhibition of αSyn aggregation. Aptamer exhibited strong inhibition of αSyn aggregation by transmission electron microscopy and Thioflavin T fluorescence.

Syntenic relationship of chromosomes in species and based on the chromosome-level genome assemblies.

The clade, to which the parasitic nematode genus belongs, contains taxa with diverse lifestyles, ranging from free-living to obligate vertebrate parasites. Reproductive strategies are also diverse in this group of nematodes, employing not only sexual reproduction but also parthenogenesis, making it an attractive group to study genome adaptation to specific conditions. An in-depth understanding of genome evolution, however, has been hampered by fragmented genome assemblies.

Advancing omics data: bridging the gap with .

Among nematodes, the free-living model organism boasts the most advanced portfolio of high-quality omics data. The resources available for parasitic nematodes, including spp., however, are lagging behind.

: omics to worm-free populations.

This article is part of the Theo Murphy meeting issue ': omics to worm-free populations'.

stepRNA: Identification of Dicer cleavage signatures and passenger strand lengths in small RNA sequences.

The enzyme Dicer is a component of many small RNA (sRNA) pathways involved in RNA processing for post-transcriptional regulation, anti-viral response and control of transposable elements. Cleavage of double-stranded RNA by Dicer produces a signature overhanging sequence at the 3' end of the sRNA sequence relative to a complementary passenger strand in a RNA duplex. There is a need for reliable tools to computationally search for Dicer cleavage signatures to help characterise families of sRNAs.

piRNA-like small RNAs target transposable elements in a Clade IV parasitic nematode.

The small RNA (sRNA) pathways identified in the model organism Caenorhabditis elegans are not widely conserved across nematodes. For example, the PIWI pathway and PIWI-interacting RNAs (piRNAs) are involved in regulating and silencing transposable elements (TE) in most animals but have been lost in nematodes outside of the C. elegans group (Clade V), and little is known about how nematodes regulate TEs in the absence of the PIWI pathway.

A microRNA-gated thgRNA platform for multiplexed activation of gene expression in mammalian cells.

To effectively reprogram cellular regulatory networks towards desired phenotypes, it is critical to have the ability to provide precise gene regulation in a spatiotemporal manner. We have previously engineered toehold-gated guide RNA (thgRNA) to enable conditional activation of dCas9-mediated transcriptional upregulation in mammalian cells using synthetic RNA triggers. Here, we demonstrate that microRNA (miR)-gated thgRNAs can be transcribed by type II RNA polymerase to allow multiplexed transcriptional activation using both mRNA and miR.

Deciphering the Design Rules of Toehold-Gated sgRNA for Conditional Activation of Gene Expression and Protein Degradation in Mammalian Cells.

A new class of toehold-gated gRNAs (thgRNAs) has been created to provide conditional gene regulation via RNA-mediated activation. However, the detailed design principles remain elusive. Here, we presented an investigation into the design rules for conditional gRNAs by systematically varying the toehold, stem, and flexible loop regions of thgRNA for optimal gene activation in HeLa cells.

Is alcohol use associated with psychological treatment attendance and clinical outcomes?

Objectives: To investigate associations between alcohol use, psychological treatment attendance, and clinical outcomes.

Methods: We analysed electronic health records for N = 7,986 patients accessing psychological treatment for common mental disorders. Data were collected for pre-treatment alcohol use (average units per week) and severity of dependence (SDS), number of therapy contacts attended, pre- and post-treatment anxiety (GAD-7), and depression (PHQ-9) symptom severity.

Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA.

Shaping Behaviors Through Institutional Support in British Higher Educational Institutions: Focusing on Employees for Sustainable Technological Change.

Technology permeates all walks of life. It has emerged as a global facilitator to improve learning and training, alleviating the temporal and spatial limitations of traditional learning systems. It is imperative to identify enablers or inhibitors of technology adoption by employees for sustainable change in education management systems.

Controlling metabolic flux by toehold-mediated strand displacement.

To maximize desired products in engineered cellular factories it is often necessary to optimize metabolic flux. While a number of works have focused on metabolic pathway enhancement through genetic regulators and synthetic scaffolds, these approaches require time-intensive design and optimization with limited versatility and capacity for scale-up. Recently, nucleic-acid nanotechnology has emerged as an encouraging approach to overcome these limitations and create systems for modular programmable control of metabolic flux.

Roles and challenges of family physicians in Uganda: A qualitative study.

Background: The World Health report (2008), the World Health Assembly (2009) and the Declaration of Astana (2018) acknowledge the significant contribution of family physicians (FPs) in clinical and primary healthcare. Given the lack of resources and low numbers of FPs coupled with the contextual nature of family medicine (FM), the scope of practice of African FPs is likely to differ from that of colleagues in America and Europe. Thus, this study explored the roles of Ugandan FPs and the challenges they face.

Sequential Changes in the Host Gut Microbiota During Infection With the Intestinal Parasitic Nematode .

Soil-transmitted helminths (STHs) are medically important parasites that infect 1. 5 billion humans globally, causing a substantial disease burden. These parasites infect the gastrointestinal tract (GIT) of their host where they co-exist and interact with the host gut bacterial flora, leading to the coevolution of the parasites, microbiota, and host organisms.

The role of intraperitoneal ropivacaine in laparoscopic appendicectomy: a prospective, double-blinded randomized control Australian study.

Background: Currently, intraoperative use of local anaesthetic is not routinely given in all laparoscopic appendicectomies. Although its use has been widely studied in laparoscopic hernia repairs, gynaecological laparoscopy and laparoscopic cholecystectomies, there are no published trials of the use of intraperitoneal local anaesthetic during laparoscopic appendicectomy in the Australasian setting. The aim of this study was to determine whether the use of intraperitoneal ropivacaine during laparoscopic appendicectomy will reduce the amount of post-operative opiate analgesia used, abdominal pain, post-operative nausea or vomiting, shoulder tip pain and length of hospital stay.

Asking for Feedback: Clinical Nurses' Perceptions of a Peer Review Program in a Community Hospital.

Objective: The purpose of this study was to understand clinical nurses' perceptions of their participation in a formal, annual peer review process at a metropolitan community hospital.

Background: Peer review is an essential component of professional nursing practice for self-regulation of the practice and promotion of quality and safety. Robust empirical evidence of formalized and effective peer review nursing processes is not evident.

New Prototype Screened Doors and Windows for Excluding Mosquitoes from Houses: A Pilot Study in Rural Gambia.

Despite compelling evidence that modern housing protects against malaria, houses in endemic areas are still commonly porous to mosquitoes. The protective efficacy of four prototype screened doors and two windows designs against mosquito house entry, their impact on indoor climate, as well as their use, durability and acceptability was assessed in a Gambian village. A baseline survey collected data on all the houses and discrete household units, each consisting of a front and back room, were selected and randomly allocated to the study arms.

A non-randomised controlled pilot study of clinical pharmacist collaborative intervention for community dwelling patients with COPD.

UK, home-based patients with COPD receive specialist care from respiratory physicians, nurses, and general practitioners (GPs), but increasing complexity of therapeutic options and a GP/Nurse workforce crisis suggests merit in testing the role of home visits by a clinical pharmacist. We conducted a non-randomised intervention study with a contemporaneous comparator group, in Glasgow (Scotland). A clinical pharmacist (working closely with a consultant respiratory physician) visited patients with COPD living at home, assessing respiratory and other co-morbid conditions, and medicines then, with patient approval, agreed treatment modifications with a consultant physician.

Automated microscopy for routine malaria diagnosis: a field comparison on Giemsa-stained blood films in Peru.

Background: Microscopic examination of Giemsa-stained blood films remains a major form of diagnosis in malaria case management, and is a reference standard for research. However, as with other visualization-based diagnoses, accuracy depends on individual technician performance, making standardization difficult and reliability poor. Automated image recognition based on machine-learning, utilizing convolutional neural networks, offers potential to overcome these drawbacks.

In Vivo Use of a Multi-DNA Aptamer-Based Payload/Targeting System To Study Dopamine Dysregulation in the Central Nervous System.

The delivery of therapeutics across the blood-brain barrier remains a considerable challenge in investigating central nervous system related processes. In this work, a liposome vehicle was surface-modified with an aptamer that binds to the transferrin receptor and was loaded with two different dopamine-binding aptamer payloads. This system was effectively used to promote the delivery of the aptamer cargo from the peripheral injection site into the brain.

Biology and genome of a newly discovered sibling species of Caenorhabditis elegans.

A 'sibling' species of the model organism Caenorhabditis elegans has long been sought for use in comparative analyses that would enable deep evolutionary interpretations of biological phenomena. Here, we describe the first sibling species of C. elegans, C.