RPL3L-containing ribosomes modulate mitochondrial activity in the mammalian heart

ABSTRACTThe existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L, a ribosomal protein (RP) paralog of RPL3 that is exclusively expressed in muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon Rpl3l depletion, RPL3 becomes upregulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-Seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L neither modulated translational efficiency nor ribosome affinity towards a specific subset of transcripts. By contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of mitochondrial activity fine-tuning. Our results demonstrate that the existence of tissue-specific RP paralogs does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.

On eco-evolutionary dynamics of phenologies in competitive communities and their robustness to climate change

Global changes currently cause temporal shifts in the favourable conditions for different phases of species life cycles. Phenologies characterizing temporal presence, may adapt through heritable evolution in response to these changes. Given a community context, this evolution may cause a change in the phenology overlap and thus a change of interspecific interactions such as competition. Using a model in which phenologies compete and coevolve, we study the conditions under which diversity emerges, as well as their annual distribution. We find that the environment richness (food quantity, light, pollinators, etc) and competition constrain the diversity and spread of phenologies. A robust pattern of phenologies distribution emerges consistent with Swedish flowering observations. Once a stable community is reached, we apply a progressive change in environmental conditions. We found that adaptation eventually restored diversity, but that the simulated change often led to numerous extinctions due to increased competition. The percentage of diversity lost depends on the speed of change and on the initial diversity. Phenologies already pre-adapted to the new environmental conditions drive the restoration of diversity after the change. We finally study a spatial version of the model in which local communities are organized along an environmental gradient. Pre-change, allowing dispersal decreases the local adaptation of phenologies to their local fixed environmental conditions. Dispersal however largely enhances the maintenance of biodiversity in changing environments, though its benefits are not homogeneous in space. Evolution remains the only rescue mechanism for southern phenotypes.

Puf6 primes 60S pre-ribosome nuclear export at low temperature

Productive ribosomal RNA (rRNA) compaction during ribosome assembly necessitates establishing correct tertiary contacts between distant secondary structure elements. Here, we quantify the response of the yeast proteome to low temperature (LT), a condition where aberrant mis-paired RNA folding intermediates accumulate. We show that, at LT, yeast cells globally boost production of their ribosome assembly machinery. We find that the LT-induced assembly factor, Puf6, binds to the nascent catalytic RNA-rich subunit interface within the 60S pre-ribosome, at a site that eventually loads the nuclear export apparatus. Ensemble Förster resonance energy transfer studies show that Puf6 mimics the role of Mg2+ to usher a unique long-range tertiary contact to compact rRNA. At LT, puf6 mutants accumulate 60S pre-ribosomes in the nucleus, thus unveiling Puf6-mediated rRNA compaction as a critical temperature-regulated rescue mechanism that counters rRNA misfolding to prime export competence.

RescueAlert-an accident detection and rescue mechanism

With the increase of vehicles and cars of different kind and the large movement that occurs every day on the roads it was natural to observe an increase in traffic accidents, but the real dilemma lies in how to make the rescue process efficient. The problem that we want to solve is the response of ambulances towards accidents and the lengthy registration process of patients in hospitals. In the above two scenarios, the manual process of calling the ambulance leads to delay in rescue of patients from an accident and the delay in registration of patient leads to delay in medication or treatment of the patient. We want to make the process more efficient by automating accident detection for increasing the efficiency of the ambulance rescue process and by sending the details of the patient before the patient reaches the hospitals for faster treatment of patients. Along with this, alert messages will be sent to the family or friends of the patients to notify them as soon as an accident is detected.

Reflection on Emergency Management in China Based on Novel Coronavirus Pneumonia Prevention and Control

In 2019, China had novel coronavirus pneumonia outbreak in Wuhan, China, which seriously threatened people’s health and affected social order and economic development. The novel coronavirus epidemic has been actively dealt with by the government. However, there are still some problems, such as weak awareness of crisis, ineffective emergency response, stagnant legal construction, unsound rumors, ineffective public opinion, insufficient material support, inefficient allocation of resources, the local officials with low ability, inadequate humanistic care and incomplete rescue mechanism. By analyzing how the government deal with the novel coronavirus pneumonia crisis, we can optimize the working mechanism, improving the working methods, and improving the government’s emergency management capability.

Prenatal diagnosis of 7 cases with uniparental disomy by utilization of single nucleotide polymorphism array

Background The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. Results Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. Conclusion The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.

Mountain Disasters and Rescue Mechanism in Nepal

Geographically, Nepal is divided into three regions, namely; the Terai, the hills, and the mountains. Nepal is prone to many types of disasters due to the various causes and one of the main causes is its geographic setting. Some disasters and hazards are prevalent to all over the country, some are area specific. Mountain and high altitude hazards are unique in nature and have distinct features and they pose several challenges for the rescue and relief operations. Disasters in mountain regions of Nepal have multi-dimensional effects on human life, property and the environment. The paper analyzes the mountain disasters, their nature and their impacts. It also focuses on the institutional as well as legal arrangements regarding disaster rescue. For this purpose, a qualitative descriptive and analytical method is applied to achieve the desired objectives of the study. This paper depends upon the secondary source of data available in several works of literature; journal articles, books, news articles, government reports, and websites. The paper finds that the frequencies of mountain disasters are low in comparison to other parts of Nepal, but they are diverse and complex. There are institutional and legal mechanisms for disaster risk reduction, but they are not adequate to respond mountain disasters effectively. All security agencies along with private sectors involving in mountain search and rescue operations do not have sufficient mountain-specific rescue units, training, and logistics.

b3galt6 Knock-Out Zebrafish Recapitulate β3GalT6-Deficiency Disorders in Human and Reveal a Trisaccharide Proteoglycan Linkage Region

Proteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediated b3galt6 knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human β3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study, therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention.