On the link between Earth tides and volcanic degassing

Long-term measurements of volcanic gas emissions conducted during the last decade suggest that under certain conditions the magnitude or chemical composition of volcanic emissions exhibits periodic variations with a period of about 2 weeks. A possible cause of such a periodicity can be attributed to the Earth tidal potential. The phenomenology of such a link has been debated for long, but no quantitative model has yet been proposed. The aim of this paper is to elucidate whether a causal link between tidal forcing and variations in volcanic degassing can be traced analytically. We model the response of a simplified magmatic system to the local tidal gravity variations and derive a periodical vertical magma displacement in the conduit with an amplitude of 0.1–1&thinsp;m, depending on the geometry and physical state of the magmatic system. We find that while the tide-induced vertical magma displacement presumably has no significant direct effect on the volatile solubility, the differential magma flow across the radial conduit profile may result in a significant increase in the bubble coalescence rate at a depth of several kilometres by up to several multiples of 10&thinsp;%. Because bubble coalescence facilitates separation of gas from magma and thus enhances volatile degassing, we argue that the derived tidal variation may propagate to a manifestation of varying volcanic degassing behaviour. The presented model provides a first basic framework which establishes an analytical understanding of the link between the Earth tides and volcanic degassing.</p

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity

SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease

Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination

The H2AX core histone variant is phosphorylated in chromatin around DNA double strand breaks (DSBs) and functions through unknown mechanisms to suppress antigen receptor locus translocations during V(D)J recombination. Formation of chromosomal coding joins and suppression of translocations involves the ataxia telangiectasia mutated and DNA-dependent protein kinase catalytic subunit serine/threonine kinases, each of which phosphorylates H2AX along cleaved antigen receptor loci. Using Abelson transformed pre–B cell lines, we find that H2AX is not required for coding join formation within chromosomal V(D)J recombination substrates. Yet we show that H2AX is phosphorylated along cleaved Igκ DNA strands and prevents their separation in G1 phase cells and their progression into chromosome breaks and translocations after cellular proliferation. We also show that H2AX prevents chromosome breaks emanating from unrepaired RAG endonuclease-generated TCR-α/δ locus coding ends in primary thymocytes. Our data indicate that histone H2AX suppresses translocations during V(D)J recombination by creating chromatin modifications that stabilize disrupted antigen receptor locus DNA strands to prevent their irreversible dissociation. We propose that such H2AX-dependent mechanisms could function at additional chromosomal locations to facilitate the joining of DNA ends generated by other types of DSBs

RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation

Interleukin 7 (IL-7) promotes pre–B cell survival and proliferation by activating the Pim1 and Akt kinases. These signals must be attenuated to induce G1 cell cycle arrest and expression of the RAG endonuclease, which are both required for IgL chain gene rearrangement. As lost IL-7 signals would limit pre–B cell survival, how cells survive during IgL chain gene rearrangement remains unclear. We show that RAG-induced DNA double-strand breaks (DSBs) generated during IgL chain gene assembly paradoxically promote pre–B cell survival. This occurs through the ATM-dependent induction of Pim2 kinase expression. Similar to Pim1, Pim2 phosphorylates BAD, which antagonizes the pro-apoptotic function of BAX. However, unlike IL-7 induction of Pim1, RAG DSB-mediated induction of Pim2 does not drive proliferation. Rather, Pim2 has antiproliferative functions that prevent the transit of pre–B cells harboring RAG DSBs from G1 into S phase, where these DNA breaks could be aberrantly repaired. Thus, signals from IL-7 and RAG DSBs activate distinct Pim kinase family members that have context-dependent activities in regulating pre–B cell proliferation and survival

Point-of-admission hypothermia among high-risk Nigerian newborns

<p>Abstract</p> <p>Background</p> <p>Facilities which manage high-risk babies should frequently assess the burden of hypothermia and strive to reduce the incidence.</p> <p>Objective</p> <p>To determine the incidence and outcome of point-of-admission hypothermia among hospitalized babies.</p> <p>Methods</p> <p>The axillary temperatures of consecutive admissions into a Nigerian Newborn Unit were recorded. Temperature <36.5°C defined hypothermia. The biodata and outcome of these babies were studied.</p> <p>Results</p> <p>Of 150 babies aged 0 to 648 hours, 93 had hypothermia with an incidence of 62%. Mild and moderate hypothermia accounted for 47.3% and 52.7% respectively. The incidence of hypothermia was highest (72.4%) among babies aged less than 24 hours. It was also higher among out-born babies compared to in-born babies (64.4% <it>vs </it>58.3%). Preterm babies had significantly higher incidence of hypothermia (82.5%) compared with 54.5% of term babies (RR = 1.51; CI = 1.21 – 1.89). The incidence of hypothermia was also highest (93.3%) among very-low-birth-weight babies.</p> <p>The Case-Fatality-Rate was significantly higher among hypothermic babies (37.6% vs 16.7%; RR = 2.26, CI = 1.14 – 4.48) and among out-born hypothermic babies (50% vs 17.1%; RR = 0.34, CI = 0.16 – 0.74). CFR was highest among hypothermic babies with severe respiratory distress, sepsis, preterm birth and asphyxia.</p> <p>Conclusion</p> <p>The high incidence and poor outcome of hypothermia among high-risk babies is important. The use of the 'warm chain' and skin-to-skin contact between mother and her infant into routine delivery services in health facilities and at home may be useful.</p

ATM Limits Incorrect End Utilization during Non-Homologous End Joining of Multiple Chromosome Breaks

Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI–resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis.

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease

Gas emissions from five volcanoes in northern Chile, and implications for the volatiles budget of the Central Volcanic Zone

This study performed the first assessment of the volcanic gas output from the Central Volcanic Zone (CVZ) of northern Chile. We present the fluxes and compositions of volcanic gases (H2O, CO2, H2, HCl, HF, and HBr) from five of the most actively degassing volcanoes in this region—Láscar, Lastarria, Putana, Ollagüe, and San Pedro—obtained during field campaigns in 2012 and 2013. The inferred gas plume compositions for Láscar and Lastarria (CO2/Stot = 0.9–2.2; Stot/HCl = 1.4–3.4) are similar to those obtained in the Southern Volcanic Zone of Chile, suggesting uniform magmatic gas fingerprint throughout the Chilean arc. Combining these compositions with our own UV spectroscopy measurements of the SO2 output (summing to ~1800 t d−1 for the CVZ), we calculate a cumulative CO2 output of 1743–1988 t d−1 and a total volatiles output of >20,200 t d−1