Precise genome editing of plants has the potential to reshape global agriculture through the targeted engineering of endogenous pathways or the introduction of new traits. To develop a CRISPR ...nuclease-based platform that would enable higher efficiencies of precise gene insertion or replacement, we screened the Cpf1 nucleases from Francisella novicida and Lachnospiraceae bacterium ND2006 for their capability to induce targeted gene insertion via homology directed repair. Both nucleases, in the presence of a guide RNA and repairing DNA template flanked by homology DNA fragments to the target site, were demonstrated to generate precise gene insertions as well as indel mutations at the target site in the rice genome. The frequency of targeted insertion for these Cpf1 nucleases, up to 8%, is higher than most other genome editing nucleases, indicative of its effective enzymatic chemistry. Further refinements and broad adoption of the Cpf1 genome editing technology have the potential to make a dramatic impact on plant biotechnology.
Blunt thoracic aortic injury, a life-threatening concern, remains the second most common cause of mortality among all non-penetrating traumatic injuries, second only to intracranial hemorrhage. ...Kinetic forces from the rapid deceleration are the impetus for the injury mechanism and are graded accordingly. Given the prevalence of trauma as a public health problem, contemporary management considerations are important.
Blunt thoracic aortic injury may be fatal if not diagnosed and treated expeditiously. Endovascular options allow safe and effective management of these dangerous injuries. This paper describes the overview of blunt thoracic aortic trauma, the epidemiology, presentation, diagnosis, and treatment options with a focus on endovascular management.
Blunt thoracic aortic injury requires a high index of suspicion based on mechanism of injury in the trauma population. Endovascular options have become the mainstay of blunt thoracic aortic injury treatment whenever feasible with satisfactory results and long-term outcomes.
Abstract
Forecast skill of numerical weather prediction (NWP) models for precipitation accumulations over California is rather limited at subseasonal time scales, and the low signal-to-noise ratio ...makes it challenging to extract information that provides reliable probabilistic forecasts. A statistical postprocessing framework is proposed that uses an artificial neural network (ANN) to establish relationships between NWP ensemble forecast and gridded observed 7-day precipitation accumulations, and to model the increase or decrease of the probabilities for different precipitation categories relative to their climatological frequencies. Adding predictors with geographic information and location-specific normalization of forecast information permits the use of a single ANN for the entire forecast domain and thus reduces the risk of overfitting. In addition, a convolutional neural network (CNN) framework is proposed that extends the basic ANN and takes images of large-scale predictors as inputs that inform local increase or decrease of precipitation probabilities relative to climatology. Both methods are demonstrated with ECMWF ensemble reforecasts over California for lead times up to 4 weeks. They compare favorably with a state-of-the-art postprocessing technique developed for medium-range ensemble precipitation forecasts, and their forecast skill relative to climatology is positive everywhere within the domain. The magnitude of skill, however, is low for week-3 and week-4, and suggests that additional sources of predictability need to be explored.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aims
To evaluate the complexity of root canal treatments accepted for treatment by postgraduate training grades at Cardiff University Dental Hospital (CUDH) using the English Commissioning Standard ...for Restorative Dentistry (ECS) in comparison with the American Association of Endodontists case complexity form (AAE) and the Restorative Index of Treatment Need (RIOTN).
Methodology
Two hundred case records were evaluated using the AAE, RIOTN and ECS scoring systems. Each case received a score from minimal to high complexity (1–3). Examiners were calibrated and inter‐examiner reliability calculated using the percentage agreement. Frequency of scores were then compared.
Results
Most cases were at level 3 and assessment varied amongst the criteria used (AAE: 99.5%, RIOTN: 65.5% and ECS: 55.5%). The AAE factor ‘endodontic treatment history’ was largely responsible for differing scores when compared with the RIOTN (78%) and ECS (64%). The RIOTN factor regarding post treatment disease (‘endodontic retreatment’) was responsible for increased complexity compared with ECS in most cases (74%). The ECS factor ‘quality of root filling’ was the most common reason (85%) for an increase in complexity compared with RIOTN.
Conclusions
Within the limitations of this service evaluation, it was possible to conclude that a high proportion of cases treated by training grades at CUDH were of a high complexity level (level 3) using the three guidelines (ECS, AAE and RIOTN). These cases were appropriate for postgraduate training under various levels of supervision and substantiated by the findings reported here. The factors responsible for a large part of difference in allocation of scores amongst the systems were ‘endodontic treatment history’, ‘root canal retreatment’ and ‘quality of root filling’.
Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania ...mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy numbers, identifying large copy number variations between species, with 200 tandem gene arrays in L. major and 132 in L. mexicana. Chromosome copy number also varied significantly between species, with nine supernumerary chromosomes in L. infantum, four in L. mexicana, two in L. braziliensis, and one in L. major. A significant bias against gene arrays on supernumerary chromosomes was shown to exist, indicating that duplication events occur more frequently on disomic chromosomes. Taken together, our data demonstrate that there is little variation in unique gene content across Leishmania species, but large-scale genetic heterogeneity can result through gene amplification on disomic chromosomes and variation in chromosome number. Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression in response to environmental conditions in the host, providing a genetic basis for disease tropism.
The incubation period for malaria parasites within the mosquito is exquisitely temperature-sensitive, so that temperature is a major determinant of malaria risk. Epidemiological models are ...increasingly used to guide allocation of disease control resources and to assess the likely impact of climate change on global malaria burdens. Temperature-based malaria transmission is generally incorporated into these models using mean monthly temperatures, yet temperatures fluctuate throughout the diurnal cycle. Here we use a thermodynamic malaria development model to demonstrate that temperature fluctuation can substantially alter the incubation period of the parasite, and hence malaria transmission rates. We find that, in general, temperature fluctuation reduces the impact of increases in mean temperature. Diurnal temperature fluctuation around means >21°C slows parasite development compared with constant temperatures, whereas fluctuation around <21°C speeds development. Consequently, models which ignore diurnal variation overestimate malaria risk in warmer environments and underestimate risk in cooler environments. To illustrate the implications further, we explore the influence of diurnal temperature fluctuation on malaria transmission at a site in the Kenyan Highlands. Based on local meteorological data, we find that the annual epidemics of malaria at this site cannot be explained without invoking the influence of diurnal temperature fluctuation. Moreover, while temperature fluctuation reduces the relative influence of a subtle warming trend apparent over the last 20 years, it nonetheless makes the effects biologically more significant. Such effects of short-term temperature fluctuations have not previously been considered but are central to understanding current malaria transmission and the consequences of climate change.
Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, ...interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10
bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.
MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).
This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.
This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
Malaria transmission is strongly influenced by environmental temperature, but the biological drivers remain poorly quantified. Most studies analyzing malaria–temperature relations, including those ...investigating malaria risk and the possible impacts of climate change, are based solely on mean temperatures and extrapolate from functions determined under unrealistic laboratory conditions. Here, we present empirical evidence to show that, in addition to mean temperatures, daily fluctuations in temperature affect parasite infection, the rate of parasite development, and the essential elements of mosquito biology that combine to determine malaria transmission intensity. In general, we find that, compared with rates at equivalent constant mean temperatures, temperature fluctuation around low mean temperatures acts to speed up rate processes, whereas fluctuation around high mean temperatures acts to slow processes down. At the extremes (conditions representative of the fringes of malaria transmission, where range expansions or contractions will occur), fluctuation makes transmission possible at lower mean temperatures than currently predicted and can potentially block transmission at higher mean temperatures. If we are to optimize control efforts and develop appropriate adaptation or mitigation strategies for future climates, we need to incorporate into predictive models the effects of daily temperature variation and how that variation is altered by climate change.
In Memoriam: Charles Chan Ambrosi, Thomas H; Jaiswal, Siddhartha; Greenblatt, Matthew B
Journal of bone and mineral research,
06/2024, Letnik:
39, Številka:
7
Journal Article
The parasites that cause malaria depend on Anopheles mosquitoes for transmission; because of this, mosquito population dynamics are a key determinant of malaria risk. Development and survival rates ...of both the Anopheles mosquitoes and the Plasmodium parasites that cause malaria depend on temperature, making this a potential driver of mosquito population dynamics and malaria transmission. We developed a temperature-dependent, stage-structured delayed differential equation model to better understand how climate determines risk. Including the full mosquito life cycle in the model reveals that the mosquito population abundance is more sensitive to temperature than previously thought because it is strongly influenced by the dynamics of the juvenile mosquito stages whose vital rates are also temperature-dependent. Additionally, the model predicts a peak in abundance of mosquitoes old enough to vector malaria at more accurate temperatures than previous models. Our results point to the importance of incorporating detailed vector biology into models for predicting the risk for vector borne diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
