Mitotic chromosomes are self-entangled and disentangle through a topoisomerase-II-dependent two-stage exit from mitosis.

The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations, and multi-contact 3C and find that, by contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interphase state during mitotic exit. Most mitotic entanglements are removed during anaphase/telophase, with remaining ones removed during early G1, in a topoisomerase-II-dependent process. Polymer models suggest a two-stage disentanglement pathway: first, decondensation of mitotic chromosomes with remaining condensin loops produces entropic forces that bias topoisomerase II activity toward decatenation. At the second stage, the loops are released, and the formation of new entanglements is prevented by lower topoisomerase II activity, allowing the establishment of unentangled and territorial G1 chromosomes. When mitotic entanglements are not removed in experiments and models, a normal interphase state cannot be acquired.

The Magellanic Corona as the key to the formation of the Magellanic Stream.

The dominant gaseous structure in the Galactic halo is the Magellanic Stream. This extended network of neutral and ionized filaments surrounds the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), the two most massive satellite galaxies of the Milky Way1-4. Recent observations indicate that the LMC and SMC are on their first passage around the Galaxy5, that the Magellanic Stream is made up of gas stripped from both clouds2,6,7 and that the majority of this gas is ionized8,9. Although it has long been suspected that tidal forces10,11 and ram-pressure stripping12,13 contributed to the formation of the Magellanic Stream, models have not been able to provide a full understanding of its origins3. Several recent developments-including the discovery of dwarf galaxies associated with the Magellanic group14-16, determination of the high mass of the LMC17, detection of highly ionized gas near stars in the LMC18,19 and predictions of cosmological simulations20,21-support the existence of a halo of warm (roughly 500,000 kelvin) ionized gas around the LMC (the 'Magellanic Corona'). Here we report that, by including this Magellanic Corona in hydrodynamic simulations of the Magellanic Clouds falling onto the Milky Way, we can reproduce the Magellanic Stream and its leading arm. Our simulations explain the filamentary structure, spatial extent, radial-velocity gradient and total ionized-gas mass of the Magellanic Stream. We predict that the Magellanic Corona will be unambiguously observable via high-ionization absorption lines in the ultraviolet spectra of background quasars lying near the LMC.

Soil microbial community structures are shaped by agricultural systems revealing little temporal variation.

Many studies in soil microbial ecology are undertaken with a single sampling event, with the influence of temporal progression rarely being considered. Under field conditions, soil samples were taken from different agricultural systems; a sown grassland to maize rotation (MC), an intensively managed permanent grassland (INT), as well as extensively managed permanent grasslands with high (EXT_HP), low to sufficient (EXT_LP) and deficient available P (EXT_DP), six times throughout the 2017 growing season. Thus, this study aimed to determine if any differences in soil microbiome structures between both sharply contrasting (MC - INT - EXT), slightly differing (EXT_HP - EXT_DP) and quite similar (EXT_HP - EXT_LP and EXT_LP - EXT_DP) agricultural systems persist through changing growth conditions within the growing season. For both fungal and bacterial community structure, the influence of agricultural system (CV = 0.256, P < 0.001 and CV = 0.145, P < 0.01, respectively) was much greater than that of temporal progression (√CV = 0.065 and 0.042, respectively, both P < 0.001). Importantly, nearly all agricultural systems persistently harbored significantly distinct fungal community structures across each of the six sampling events (all at least P < 0.05). There were not as many pairwise differences in bacterial community structure between the agricultural systems, but some did persist (MC and EXT_HP âˆ¼ EXT_DP, all P < 0.001). Additionally, persistent indicator fungal OTUs (IndVal >0.7, P ≤ 0.05) associated to each agricultural system (except EXT_LP) were found in each of the six sampling events. These results highlight the temporal stability of pairwise differences in soil microbiome structures between established agricultural systems through changing plant growth conditions, even between those with a comparable management regime. This is a highly relevant finding in informing the sampling strategy of studies in soil microbial ecology as well as for designing efficient soil biodiversity monitoring systems.

Symptoms and laboratory manifestations of mild COVID-19 in a repatriated cruise ship cohort.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

OPTN/SRTR 2018 Annual Data Report: Pancreas.

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.

Polypharmacy and potential drug-drug interactions for people with HIV in the UK from the Climate-HIV database.

OBJECTIVES: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV. METHODS: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. RESULTS: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0-2) and 2 (1-5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. CONCLUSIONS: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.

Photon Statistics of Filtered Resonance Fluorescence.

Spectral filtering of resonance fluorescence is widely employed to improve single photon purity and indistinguishability by removing unwanted backgrounds. For filter bandwidths approaching the emitter linewidth, complex behavior is predicted due to preferential transmission of components with differing photon statistics. We probe this regime using a Purcell-enhanced quantum dot in both weak and strong excitation limits, finding excellent agreement with an extended sensor theory model. By changing only the filter width, the photon statistics can be transformed between antibunched, bunched, or Poissonian. Our results verify that strong antibunching and a subnatural linewidth cannot simultaneously be observed, providing new insight into the nature of coherent scattering.

Abdominal adiposity assessed using CT angiography associates with acute kidney injury after trans-catheter aortic valve replacement.

AIM: To determine if there is an association between area-based visceral abdominal adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAT), and abdominal circumference measured on computed tomography (CT) angiography before trans-catheter aortic valve replacement (TAVR) and post-TAVR acute kidney injury (AKI). MATERIALS AND METHODS: In this retrospective cohort study of 106 TAVR patients, SAT and VAT areas and abdominal circumference was measured on a single CT section at L4 vertebral level. Univariate comparisons between patients who did and did not develop AKI were undertaken for radiological measurements. Multivariable logistic regression was used to assess association between CT measurements and the development of post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients (19%). In univariate comparisons, body mass index (BMI) did not differ significantly between patients who did and did not develop AKI (p=0.14); however, VAT+SAT (443.2±163.7 versus 351±168.7 cm2; p=0.03), VAT (213.9±110.6 versus 153.9±96.1 cm2; p=0.03), and outer abdominal circumference (100.2±14.4 cm versus 91.8±13.3 cm; p=0.02) were significantly higher in the patients who did not develop post-TAVR AKI. These three measures on pre-TAVR CT angiogram remained significantly associated with reduced post-TAVR AKI with a lower incidence of post-TAVR AKI after multivariable adjustment for pre-TAVR estimated glomerular filtration rate and patient height (p<0.05). CONCLUSION: This study found that increased abdominal obesity as assessed by measures on pre-TAVR CT angiogram is associated with a significantly lower incidence of AKI.

OPTN/SRTR 2017 Annual Data Report: Pancreas.

In 2017, 1492 patients were added to the pancreas transplant waiting list, 964 listed as active, a slight increase from 2016. This is significant because for the first time in the past decade, the steady downward trend in additions to the waiting list has been reversed. Proportions of pancreas donors with cerebrovascular accident as cause of death decreased, with a concomitant increase in proportions with anoxia and head trauma. This is partly a result of the national opioid crisis, and it reflects increasing use of younger donors for pancreas transplant. The 2017 outcome report remains compromised by previous variation in reporting graft failure. Although the OPTN Pancreas Transplantation Committee has approved more precise definitions of pancreas graft failure, implementation of these definitions took place recently, and the data are not reflected in this report.

Light Scattering from Solid-State Quantum Emitters: Beyond the Atomic Picture.

Coherent scattering of light by a single quantum emitter is a fundamental process at the heart of many proposed quantum technologies. Unlike atomic systems, solid-state emitters couple to their host lattice by phonons. Using a quantum dot in an optical nanocavity, we resolve these interactions in both time and frequency domains, going beyond the atomic picture to develop a comprehensive model of light scattering from solid-state emitters. We find that even in the presence of a low-Q cavity with high Purcell enhancement, phonon coupling leads to a sideband that is completely insensitive to excitation conditions and to a nonmonotonic relationship between laser detuning and coherent fraction, both of which are major deviations from atomlike behavior.

Tunable Photon Statistics Exploiting the Fano Effect in a Waveguide.

A strong optical nonlinearity arises when coherent light is scattered by a semiconductor quantum dot coupled to a nanophotonic waveguide. We exploit the Fano effect in such a waveguide to control the phase of the quantum interference underpinning the nonlinearity, experimentally demonstrating a tunable quantum optical filter which converts a coherent input state into either a bunched or an antibunched nonclassical output state. We show theoretically that the generation of nonclassical light is predicated on the formation of a two-photon bound state due to the interaction of the input coherent state with the quantum dot. Our model demonstrates that the tunable photon statistics arise from the dependence of the sign of two-photon interference (either constructive or destructive) on the detuning of the input relative to the Fano resonance.

Nonreciprocal Transmission and Reflection of a Chirally Coupled Quantum Dot.

We report strongly nonreciprocal behavior for quantum dot exciton spins coupled to nanophotonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the propagation direction is found for a chirally coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions, respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment.

OPTN/SRTR 2016 Annual Data Report: Pancreas.

The number of pancreas transplants performed in the United States increased by 7.0% in 2016 over the previous year, the first such increase in more than a decade, largely attributable to an increase in simultaneous kidney pancreas transplants. Transplant rates increased in 2016, and mortality on the waiting list decreased. The declining enthusiasm for pancreas after kidney (PAK) transplants persisted. The uniform definition of graft failure was approved by the OPTN Board of Directors in 2015 and will be implemented in early 2018. Meanwhile, SRTR continues to refrain from reporting pancreas graft failure data. The OPTN/UNOS Pancreas Transplantation Committee is seeking to broaden allocation of pancreata across compatible ABO blood types in a proposal out for public comment July 31 to October 2, 2017. A new initiative to provide guidance on the benefits of PAK transplants is also out for public comment.

No country for old livers? Examining and optimizing the utilization of elderly liver grafts.

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.

Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology.

Children with an anxious temperament are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression and co-morbid substance abuse. Individuals with extreme anxious temperament often show persistent distress in the absence of immediate threat and this contextually inappropriate anxiety predicts future symptom development. Despite its clear clinical relevance, the neural circuitry governing the maladaptive persistence of anxiety remains unclear. Here, we used a well-established nonhuman primate model of childhood temperament and high-resolution 18fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to understand the neural systems governing persistent anxiety and to clarify their relevance to early-life phenotypic risk. We focused on BI, a core component of anxious temperament, because it affords the moment-by-moment temporal resolution needed to assess contextually appropriate and inappropriate anxiety. From a pool of 109 peri-adolescent rhesus monkeys, we formed groups characterized by high or low levels of BI, as indexed by freezing in response to an unfamiliar human intruder's profile. The high-BI group showed consistently elevated signs of anxiety and wariness across >2 years of assessments. At the time of brain imaging, 1.5 years after initial phenotyping, the high-BI group showed persistently elevated freezing during a 30-min 'recovery' period following an encounter with the intruder-more than an order of magnitude greater than the low-BI group-and this was associated with increased metabolism in the bed nucleus of the stria terminalis, a key component of the central extended amygdala. These observations provide a neurobiological framework for understanding the early phenotypic risk to develop anxiety-related psychopathology, for accelerating the development of improved interventions, and for understanding the origins of childhood temperament.

An outbreak of Shiga toxin-producing Escherichia coli O157:H7 associated with contaminated salad leaves: epidemiological, genomic and food trace back investigations.

In August 2015, Public Health England detected an outbreak of Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 caused by contaminated salad leaves in a mixed leaf prepacked salad product from a national retailer. The implicated leaves were cultivated at five different farms and the zoonotic source of the outbreak strain was not determined. In March 2016, additional isolates from new cases were identified that shared a recent common ancestor with the outbreak strain. A case-case study involving the cases identified in 2016 revealed that ovine exposures were associated with illness (n = 16; AOR 8·24; 95% CI 1·55-39·74). By mapping the recent movement of sheep and lambs across the United Kingdom, epidemiological links were established between the cases reporting ovine exposures. Given the close phylogenetic relationship between the outbreak strain and the isolates from cases with ovine exposures, it is plausible that ovine faeces may have contaminated the salad leaves via untreated irrigation water or run-off from fields nearby. Timely and targeted veterinary and environmental sampling should be considered during foodborne outbreaks of STEC, particularly where ready to eat vegetables and salads are implicated.

An assessment of the microbiological quality and safety of raw drinking milk on retail sale in England.

AIMS: This study aimed to review the microbiological results for raw drinking milk (RDM) samples submitted to Public Health England laboratories between 2014 and 2016 in order to produce up-to-date data on the microbiological safety of RDM and inform future risk assessments on its sale. METHODS AND RESULTS: A total of 902 samples of RDM were collected from retail sale in England for microbiological examination. Overall, 454 of 770 samples (59·0%) taken for routine monitoring were of a satisfactory quality, whilst eight (1·0%) were 'unsatisfactory and potentially injurious to health' due to the presence of Shiga toxin-producing Escherichia coli, Campylobacter or elevated levels of Listeria monocytogenes or coagulase-positive staphylococci. In contrast, 16 of 114 (14·0%) of samples taken in follow-up to a previous unsatisfactory result and 5 of 18 (27·8%) of samples related to illness were potentially injurious. A total of 229 of 902 samples (25·4%) gave unsatisfactory results due to elevated aerobic colony counts and/or coliforms, whilst 139 of 902 samples (15·4%) were of borderline quality due to coagulase-positive staphylococci. Listeria monocytogenes was detected at levels of <100 CFU per ml in 66 of 902 samples (7·3%) and other Listeria species in 44 of 902 samples (4·9%). CONCLUSIONS: Pathogens and/or indicators of poor hygiene were present in almost half of samples examined. Cows' milk samples gave a significantly greater proportion of unsatisfactory results compared to milk from other species (i.e. goat, sheep, buffalo, camel). SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate the importance of maintaining strict controls on the production and sale of this product.

The effect of local hydrodynamics on the spatial extent and morphology of cold-water coral habitats at Tisler Reef, Norway.

This study demonstrates how cold-water coral morphology and habitat distribution are shaped by local hydrodynamics, using high-definition video from Tisler Reef, an inshore reef in Norway. A total of 334 video frames collected on the north-west (NW) and south-east (SE) side of the reef were investigated for Lophelia pertusa coral cover and morphology and for the cover of the associated sponges Mycale lingua and Geodia sp. Our results showed that the SE side was a better habitat for L. pertusa (including live and dead colonies). Low cover of Geodia sp. was found on both sides of Tisler Reef. In contrast, Mycale lingua had higher percentage cover, especially on the NW side of the reef. Bush-shaped colonies of L. pertusa with elongated branches were the most abundant coral morphology on Tisler Reef. The highest abundance and density of this morphology were found on the SE side of the reef, while a higher proportion of cauliflower-shaped corals with short branches were found on the NW side. The proportion of very small L. pertusa colonies was also significantly higher on the SE side of the reef. The patterns in coral spatial distribution and morphology were related to local hydrodynamics-there were more frequent periods of downwelling currents on the SE side-and to the availability of suitable settling substrates. These factors make the SE region of Tisler Reef more suitable for coral growth. Understanding the impact of local hydrodynamics on the spatial extent and morphology of coral, and their relation to associated organisms such as sponges, is key to understanding the past and future development of the reef.

Bioethics education in Democratic Republic of Congo: Experiences and challenges.

In regions marked by socio-economic turmoil, the task of teaching bioethics to health professionals and researchers can be more challenging than elsewhere. To demonstrate this, in this article we describe some of our teaching experiences in the Democratic Republic of Congo over the past decade. A first difficulty is linguistic. Anglo-Saxon language and culture largely dominates the field of bioethics, complicating teaching and education for those who do not master the language. A second obstacle is conceptual. Bioethics is often misunderstood as reflection on technological developments in medicine, which distorts its objectives and narrows its scope, particularly in resource-constrained settings. A third difficulty is cultural and political. Ethics in this setting is difficult to distinguish from common morality and the work of moralists, who comment on problems in medicine from a religious standpoint. Moreover, when interacting with communities and institutions that are strongly hierarchical, the critical stance of bioethics can give rise to resistance and rejection. These are among the array of difficulties that undoubtedly have given rise to sharp critiques of bioethics training initiatives in developing countries, where the introduction of bioethics has been depicted as a form of Western imperialism. While taking these criticisms seriously, our experiences in the field show how these seemingly insurmountable difficulties can be transformed into (more or less) manageable challenges.

Dans les régions marquées par un contexte socioéconomique difficile, les difficultés sont plus nombreuses qu'ailleurs pour ceux qui se donnent pour tâche de former à la réflexion éthique les professionnels de la santé et les chercheurs. Pour le montrer, nous évoquons dans cet article nos expériences en République Démocratique du Congo. Une première difficulté est à chercher du côté linguistique. En effet, la langue et la culture anglo-saxonnes dominent largement la discipline, compliquant la tâche de ceux qui maîtrisent mal l'anglais. Unedeuxième difficulté à surmonter est d'ordre conceptuel. Les objectifs et le champ d'application de la bioéthique sont souvent mal compris, ce qui peut conduire à confondre les spécialistesde la discipline tantôt avec des moralistes surtout préoccupés par le progrès biotechnologique, tantôt avec des référents religieux. La troisième difficulté évoquée est de nature politique et culturelle. Lorsqu'elle entre en interaction avec des communautés très hiérarchisées et conservatrices, la posture critique de la bioéthique peut susciter des réactions de rejet. Ce sont sans doute ces difficultés qui ont alimenté certaines critiques acerbes sur la pertinence des formations à l'éthique dans des zones marquées par les urgences sanitaires et alimentaires ou certaines accusations présentant ces démarches comme un avatar de plus de l'impérialisme occidental. Tout en prenant au sérieux ces difficultés, nous montrons par nos expériences qu'elles peuvent être transformées en défis à relever.