Concurrent pulmonary zygomycosis and Mycobacterium tuberculosis infection: a case report

A non-smoking 77-year old gentleman of Indian origin was admitted with a 4-month history of intermittent night sweats, haemoptysis and 6 kg of weight loss. CT scan of thorax demonstrated a 2.5 cm mass in the right middle lobe with multiple small nodules within the right lung and confirmed the presence of mediastinal and hilar lymph nodes

Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability

Naturally-occurring single α-helices (SAHs), are rich in Arg (R), Glu (E) and Lys (K) residues, and stabilized by multiple salt bridges. Understanding how salt bridges promote their stability is challenging as SAHs are long and their sequences highly variable. Thus, we designed and tested simple de novo 98-residue polypeptides containing 7-residue repeats (AEEEXXX, where X is K or R) expected to promote salt-bridge formation between Glu and Lys/Arg. Lys-rich sequences (EK3 (AEEEKKK) and EK2R1 (AEEEKRK)) both form SAHs, of which EK2R1 is more helical and thermo-stable suggesting Arg increases stability. Substituting Lys with Arg (or vice versa) in the naturally-occurring myosin-6 SAH similarly increased (or decreased) its stability. However, Arg-rich de novo sequences (ER3 (AEEERRR) and EK1R2 (AEEEKRR)) aggregated. Combining a PDB analysis with molecular modelling provides a rational explanation, demonstrating that Glu and Arg form salt bridges more commonly, utilize a wider range of rotamer conformations, and are more dynamic than Glu–Lys. This promiscuous nature of Arg helps explain the increased propensity of de novo Arg-rich SAHs to aggregate. Importantly, the specific K:R ratio is likely to be important in determining helical stability in de-novo and naturally-occurring polypeptides, giving new insight into how single α-helices are stabilized

Evaluating the Potential Effectiveness of Compensatory Mitigation Strategies for Marine Bycatch

Conservationists are continually seeking new strategies to reverse population declines and safeguard against species extinctions. Here we evaluate the potential efficacy of a recently proposed approach to offset a major anthropogenic threat to many marine vertebrates: incidental bycatch in commercial fisheries operations. This new approach, compensatory mitigation for marine bycatch (CMMB), is conceived as a way to replace or reduce mandated restrictions on fishing activities with compensatory activities (e.g., removal of introduced predators from islands) funded by levies placed on fishers. While efforts are underway to bring CMMB into policy discussions, to date there has not been a detailed evaluation of CMMB's potential as a conservation tool, and in particular, a list of necessary and sufficient criteria that CMMB must meet to be an effective conservation strategy. Here we present a list of criteria to assess CMMB that are tied to critical ecological aspects of the species targeted for conservation, the range of possible mitigation activities, and the multi-species impact of fisheries bycatch. We conclude that, overall, CMMB has little potential for benefit and a substantial potential for harm if implemented to solve most fisheries bycatch problems. In particular, CMMB is likely to be effective only when applied to short-lived and highly-fecund species (not the characteristics of most bycatch-impacted species) and to fisheries that take few non-target species, and especially few non-seabird species (not the characteristics of most fisheries). Thus, CMMB appears to have limited application and should only be implemented after rigorous appraisal on a case-specific basis; otherwise it has the potential to accelerate declines of marine species currently threatened by fisheries bycatch

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Gene expression divergence in yeast is coupled to evolution of DNA-encoded nucleosome organization

Eukaryotic transcription occurs within a chromatin environment, whose organization plays an important regulatory role and is partly encoded in cis by the DNA sequence itself1-6. Here, we examine whether evolutionary changes in gene expression are linked to changes in the DNA-encoded nucleosome organization of promoters. We find that in aerobic yeast species, where cellular respiration genes are active under typical growth conditions, the promoter sequences of these genes encode a relatively open (nucleosome-depleted) chromatin organization. This nucleosome-depleted organization requires only DNA sequence information, is independent of any co-factors and of transcription, and is a general property of growth-related genes. In contrast, in anaerobic yeast species, where cellular respiration genes are inactive under typical growth conditions, respiration gene promoters encode relatively closed (nucleosome-occupied) chromatin organizations. Thus, our results suggest a previously unidentified genetic mechanism underlying phenotypic diversity, consisting of DNA sequence changes that directly alter the DNA-encoded nucleosome organization of promoters

The DNA-encoded nucleosome organization of a eukaryotic genome

Nucleosome organization is critical for gene regulation1. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers2, competition with site-specific DNA-binding proteins3, and the DNA sequence preferences of the nucleosomes themselves4-8. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo7,9-11, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for ∼40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo