The application of next-generation sequencing to study congenital heart disease (CHD) is increasingly providing new insights into the causes and mechanisms of this prevalent birth anomaly. ...Whole-exome sequencing analysis identifies damaging gene variants altering single or contiguous nucleotides that are assigned pathogenicity based on statistical analyses of families and cohorts with CHD, high expression in the developing heart and depletion of damaging protein-coding variants in the general population. Gene classes fulfilling these criteria are enriched in patients with CHD and extracardiac abnormalities, evidencing shared pathways in organogenesis. Developmental single-cell transcriptomic data demonstrate the expression of CHD-associated genes in particular cell lineages, and emerging insights indicate that genetic variants perturb multicellular interactions that are crucial for cardiogenesis. Whole-genome sequencing analyses extend these observations, identifying non-coding variants that influence the expression of genes associated with CHD and contribute to the estimated ~55% of unexplained cases of CHD. These approaches combined with the assessment of common and mosaic genetic variants have provided a more complete knowledge of the causes and mechanisms of CHD. Such advances provide knowledge to inform the clinical care of patients with CHD or other birth defects and deepen our understanding of the complexity of human development. In this Review, we highlight known and candidate CHD-associated human genes and discuss how the integration of advances in developmental biology research can provide new insights into the genetic contributions to CHD.
Bacterial CRISPR systems have been widely adopted to create operator-specified site-specific nucleases. Such nuclease action commonly results in loss-of-function alleles, facilitating functional ...analysis of genes and gene families We conducted a systematic comparison of components and T-DNA architectures for CRISPR-mediated gene editing in Arabidopsis, testing multiple promoters, terminators, sgRNA backbones and Cas9 alleles. We identified a T-DNA architecture that usually results in stable (i.e. homozygous) mutations in the first generation after transformation. Notably, the transcription of sgRNA and Cas9 in head-to-head divergent orientation usually resulted in highly active lines. Our Arabidopsis data may prove useful for optimization of CRISPR methods in other plants.
The Pyrogenic Carbon Cycle Bird, Michael I; Wynn, Jonathan G; Saiz, Gustavo ...
Annual review of earth and planetary sciences,
05/2015, Letnik:
43, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Pyrogenic carbon (PyC; includes soot, char, black carbon, and biochar) is produced by the incomplete combustion of organic matter accompanying biomass burning and fossil fuel consumption. PyC is ...pervasive in the environment, distributed throughout the atmosphere as well as soils, sediments, and water in both the marine and terrestrial environment. The physicochemical characteristics of PyC are complex and highly variable, dependent on the organic precursor and the conditions of formation. A component of PyC is highly recalcitrant and persists in the environment for millennia. However, it is now clear that a significant proportion of PyC undergoes transformation, translocation, and remineralization by a range of biotic and abiotic processes on comparatively short timescales. Here we synthesize current knowledge of the production, stocks, and fluxes of PyC as well as the physical and chemical processes through which it interacts as a dynamic component of the global carbon cycle.
Plant immune networks Ngou, Bruno Pok Man; Jones, Jonathan D.G.; Ding, Pingtao
Trends in plant science,
March 2022, 2022-03-00, 20220301, Letnik:
27, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Plants have both cell-surface and intracellular receptors to recognize diverse self- and non-self molecules. Cell-surface pattern recognition receptors (PRRs) recognize extracellular ...pathogen-/damage-derived molecules or apoplastic pathogen-derived effectors. Intracellular nucleotide-binding leucine-rich repeat proteins (NLRs) recognize pathogen effectors. Activation of both PRRs and NLRs elevates defense gene expression and accumulation of the phytohormone salicylic acid (SA), which results in SA-dependent transcriptional reprogramming. These receptors, together with their coreceptors, form networks to mediate downstream immune responses. In addition, cell-surface and intracellular immune systems are interdependent and function synergistically to provide robust resistance against pathogens. Here, we summarize the interactions between these immune systems and attempt to provide a holistic picture of plant immune networks. We highlight current challenges and discuss potential new research directions.
Plant immunity is activated by PAMPs, effectors, and further enhanced by elevated SA, which are mediated by PRRs, NLRs, and SA receptors (NPR proteins), respectively.PRRs, NLRs, and NPR proteins interact genetically to mediate immune signals and activate robust immune outputs.Models are being elaborated for the crosstalk between PRRs, NLRs, and SA signaling.Different immune systems interact with each other both locally and systemically.
Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics. Administration of OVs to cancer-bearing hosts induces two distinct immunities: antiviral and antitumor. While antitumor ...immunity is beneficial, antiviral immune responses are often considered detrimental for the efficacy of OV-based therapy. The existing dogma postulates that anti-OV immune responses restrict viral replication and spread, and thus reduce direct OV-mediated killing of cancer cells. Accordingly, a myriad of therapeutic strategies aimed at mitigating anti-OV immune responses is presently being tested. Here, we advocate that OV-induced antiviral immune responses hold intrinsic anticancer benefits and are essential for establishing clinically desired antitumor immunity. Thus, to achieve the optimal efficacy of OV-based cancer immunotherapies, strategic management of anti-OV immune responses is of critical importance.
OVs can preferentially infect and kill malignant cancer cells, without imparting similar lytic effects on normal cells.
In addition to their direct oncolytic activity, OVs can awaken the otherwise suppressed immune system of cancer-bearing hosts and consequently promote beneficial antitumor immunity. This is an indispensable part of OV-based cancer therapies.
The antiviral immune response induced by OVs restricts viral replication and spread, and is often considered detrimental for the efficacy of therapy as it can prematurely curtail direct oncolytic activities.
However, antiviral immune responses induced by OVs can reverse tumor-mediated suppression of innate and adaptive immunity, and are thus essential for the development of clinically desired OV-induced antitumor responses.
Non-prey foods are an integral component of the diets of most predaceous coccinellids. Under field conditions, numerous coccinellids consume nectar, honeydew, pollen, fruit, vegetation, and fungus. ...These non-prey foods are used by coccinellids to increase survival when prey is scarce, reduce mortality during diapause, fuel migration, and enhance reproductive capacity. Each of these non-prey foods has unique nutritional and defensive characteristics that influence its suitability for lady beetles. Quantitatively, nutrient and energy contents of these foods are often competitive with, or even exceed that, present in prey. Meta-analyses of literature were used to assess whether (1) some non-prey foods and prey are equivalent foods for coccinellids, and (2) prey-only diets and mixed diets involving prey and non-prey foods are equally suitable for coccinellids. Response variables were categorized as larval performance (e.g., development time, weight at eclosion), adult performance (e.g., adult longevity, weight change), and reproduction (e.g., fecundity, oviposition period). The analyses revealed that pollen is inferior to prey for supporting larval and adult performance, but that adult performance in sugar-fed adults was equal to that of prey-fed adults (although sugar alone does not support reproduction). Larval performance was enhanced substantially when they were reared on mixed diets compared to prey-only diets. Adding sugar to mixed diets strongly improved adult performance and reproduction over prey-only diets, but this was not the case with pollen in mixed diets. These results suggest that coccinellid larvae have more stringent nutritional requirements than adults, and that non-prey foods provide unique nutrients that enhance prey-only diets. Moreover, it suggests that simple carbohydrates are important dietary constituents capable of enhancing both adult performance and reproduction, although it is important to note that a range of prey species of variable quality for coccinellids are evaluated in this database. The literature review presented here suggests that non-prey foods are a critical component of coccinellid nutritional ecology, and may influence the success of conservation biological control programs.
The population growth rate is an important characteristic of any cell culture. During sustained experiments, the growth rate may vary due to competition or adaptation. For instance, in presence of a ...toxin or a drug, an increasing growth rate indicates that the cells adapt and become resistant. Consequently, time-dependent growth rates are fundamental to follow on the adaptation of cells to a changing evolutionary landscape. However, as there are no tools to calculate the time-dependent growth rate directly by cell counting, it is common to use only end point measurements of growth rather than tracking the growth rate continuously.
We present a computer program for inferring the growth rate over time in suspension cells using nothing but cell counts, which can be measured non-destructively. The program was tested on simulated and experimental data. Changes were observed in the initial and absolute growth rates, betraying resistance and adaptation.
For experiments where adaptation is expected to occur over a longer time, our method provides a means of tracking growth rates using data that is normally collected anyhow for monitoring purposes. The program and its documentation are freely available at https://github.com/Sandalmoth/ratrack under the permissive zlib license.
New sequencing methods generate data that can allow the assembly of microbial genome sequences in days. With such revolutionary advances in technology come new challenges in methodologies and ...informatics. In this article, we review the capabilities of high-throughput sequencing technologies and discuss the many options for getting useful information from the data.
Background
Laparoscopic subtotal cholecystectomy (LSC) is a safe bailout procedure in situations when dissection of "critical view of safety" is not possible. After the proposed classification of ...subtotal cholecystectomy into "fenestrating" and "reconstituting" techniques in 2016, a comparative review of the outcomes of both methods is timely.
Methods
A literature search of the PubMed, Cochrane Library, and Web of Science database was conducted up to January 31, 2020 for studies that reported LSC. Studies reporting LSC only in patients with Mirizzi syndrome or xanthogranulomatous cholecystitis were excluded. Our analysis includes 39 studies with 1784 cases of LSC. We report a comparison of outcomes between reconstituting and fenestrating LSC on 1505 cases 935 reconstituting (62.1%) and 570 fenestrating (37.9%).
Results
Following LSC, the rate of open conversion is 7.7%, hemorrhage is 0.4%, bile duct injury is 0.3%, bile leak is 15.4%, retained stone is 4.6%, subhepatic or subphrenic collection is 2.9%, superficial surgical site infection is 2.0% and 30-day mortality is 0.2%. 8.8% of patients required postoperative endoscopic retrograde cholangiopancreatography (ERCP), 1.1% required percutaneous intervention, and 2.2% required reoperation. Compared to reconstituting LSC, fenestrating LSC has a higher incidence of open conversion (
n
= 58, 10.2% vs.
n
= 43, 4.6%,
p
< 0.001), retained stones (
n
= 38, 6.7% vs.
n
= 38, 4.1%,
p
= 0.0253), subhepatic or subphrenic collections (
n
= 33, 5.8% vs.
n
= 13, 1.4%,
p
< 0.001), superficial surgical site infections (
n
= 18, 3.2% vs.
n
= 14, 1.5%,
p
= 0.0303), postoperative ERCP (
n
= 82, 14.4% vs.
n
= 62, 6.6%,
p
< 0.001), and need for reoperation (
n
= 20, 3.5% vs.
n
= 12, 1.3%,
p
< 0.001).
Conclusions
Although reconstituting LSC has better outcomes, both techniques are complementary. Intraoperative findings and surgical expertise impact the choice.
Graphical abstract Highlights ► Oxidative stress is thought to contribute to the pathogenesis of glaucoma. ► Mitochondria are a central source and target of oxidative stress. ► Signs of oxidative ...stress and damage are present in glaucomatous tissue. ► Reactive oxygen species can cause retinal ganglion cell death directly or indirectly. ► Mitochondrial antioxidants may improve disease outcomes in glaucoma.
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