Evolution of mal ABC transporter operons in the Thermococcales and Thermotogales

<p>Abstract</p> <p>Background</p> <p>The <it>mal </it>genes that encode maltose transporters have undergone extensive lateral transfer among ancestors of the archaea <it>Thermococcus litoralis </it>and <it>Pyrococcus furiosus</it>. Bacterial hyperthermophiles of the order <it>Thermotogales </it>live among these archaea and so may have shared in these transfers. The genome sequence of <it>Thermotoga maritima </it>bears evidence of extensive acquisition of archaeal genes, so its ancestors clearly had the capacity to do so. We examined deep phylogenetic relationships among the <it>mal </it>genes of these hyperthermophiles and their close relatives to look for evidence of shared ancestry.</p> <p>Results</p> <p>We demonstrate that the two maltose ATP binding cassette (ABC) transporter operons now found in <it>Tc. litoralis </it>and <it>P. furiosus </it>(termed <it>mal </it>and <it>mdx </it>genes, respectively) are not closely related to one another. The <it>Tc. litoralis </it>and <it>P. furiosus mal </it>genes are most closely related to bacterial <it>mal </it>genes while their respective <it>mdx </it>genes are archaeal. The genes of the two <it>mal </it>operons in <it>Tt. maritima </it>are not related to genes in either of these archaeal operons. They are highly similar to one another and belong to a phylogenetic lineage that includes <it>mal </it>genes from the enteric bacteria. A unique domain of the enteric MalF membrane spanning proteins found also in these <it>Thermotogales </it>MalF homologs supports their relatively close relationship with these enteric proteins. Analyses of genome sequence data from other <it>Thermotogales </it>species, <it>Fervidobacterium nodosum</it>, <it>Thermosipho melanesiensis</it>, <it>Thermotoga petrophila</it>, <it>Thermotoga lettingae</it>, and <it>Thermotoga neapolitana</it>, revealed a third apparent <it>mal </it>operon, absent from the published genome sequence of <it>Tt. maritima </it>strain MSB8. This third operon, <it>mal3</it>, is more closely related to the <it>Thermococcales</it>' bacteria-derived <it>mal </it>genes than are <it>mal1 </it>and <it>mal2</it>. <it>F. nodosum</it>, <it>Ts. melanesiensis</it>, and <it>Tt. lettingae </it>have only one of the <it>mal1-mal2 </it>paralogs. The <it>mal2 </it>operon from an unknown species of <it>Thermotoga </it>appears to have been horizontally acquired by a <it>Thermotoga </it>species that had only <it>mal1</it>.</p> <p>Conclusion</p> <p>These data demonstrate that the <it>Tc. litoralis </it>and <it>P. furiosus mdx </it>maltodextrin transporter operons arose in the <it>Archaea </it>while their <it>mal </it>maltose transporter operons arose in a bacterial lineage, but not the same lineage as the two maltose transporter operons found in the published <it>Tt. maritima </it>genome sequence. These <it>Tt. maritima </it>maltose transporters are phylogenetically and structurally similar to those found in enteric bacteria and the <it>mal2 </it>operon was horizontally transferred within the <it>Thermotoga </it>lineage. Other <it>Thermotogales </it>species have a third <it>mal </it>operon that is more closely related to the bacterial <it>Thermococcales mal </it>operons, but the data do not support a recent horizontal sharing of that operon between these groups.</p

Darwinian Data Structure Selection

Data structure selection and tuning is laborious but can vastly improve an application's performance and memory footprint. Some data structures share a common interface and enjoy multiple implementations. We call them Darwinian Data Structures (DDS), since we can subject their implementations to survival of the fittest. We introduce ARTEMIS a multi-objective, cloud-based search-based optimisation framework that automatically finds optimal, tuned DDS modulo a test suite, then changes an application to use that DDS. ARTEMIS achieves substantial performance improvements for \emph{every} project in $5$ Java projects from DaCapo benchmark, $8$ popular projects and $30$ uniformly sampled projects from GitHub. For execution time, CPU usage, and memory consumption, ARTEMIS finds at least one solution that improves \emph{all} measures for $86\%$ ($37/43$) of the projects. The median improvement across the best solutions is $4.8\%$, $10.1\%$, $5.1\%$ for runtime, memory and CPU usage. These aggregate results understate ARTEMIS's potential impact. Some of the benchmarks it improves are libraries or utility functions. Two examples are gson, a ubiquitous Java serialization framework, and xalan, Apache's XML transformation tool. ARTEMIS improves gson by $16.5$\%, $1\%$ and $2.2\%$ for memory, runtime, and CPU; ARTEMIS improves xalan's memory consumption by $23.5$\%. \emph{Every} client of these projects will benefit from these performance improvements.Comment: 11 page

Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n=12), acute ischemic stroke (n=15), and transient tachypnea of the newborn (n=48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0–12, 12–36, and 36–60 h after birth) were collected, and neutrophil- to-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy+total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy+total-body cooling) revealed that absolute lymphocyte count changes occurring at 0–12 h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic- ischemic encephalopathy in neonates is warranted

Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy+total-body cooling (n=26), hypoxic-ischemic encephalopathy (n=12), acute ischemic stroke (n=15), and transient tachypnea of the newborn (n=48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0–12, 12–36, and 36–60 h after birth) were collected, and neutrophilto-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy+total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy+total-body cooling) revealed that absolute lymphocyte count changes occurring at 0–12h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxicischemic encephalopathy in neonates is warranted

Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury.

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = 48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0-12, 12-36, and 36-60 h after birth) were collected, and neutrophil-to-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy + total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body cooling) revealed that absolute lymphocyte count changes occurring at 0-12 h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxic-ischemic encephalopathy in neonates is warranted

A qualitative investigation of the impact of coronavirus disease 2019 (COVID-19) on emergency physicians\u27 emotional experiences and coping strategies

Study objective Throughout the coronavirus disease 2019 (COVID-19) pandemic, emergency physicians in the United States have faced unprecedented challenges, risks, and uncertainty while caring for patients in an already vulnerable healthcare system. As such, the pandemic has exacerbated high levels of negative emotions and burnout among emergency physicians, but little systematic qualitative work has documented these phenomena. The purpose of this qualitative investigation was to study emergency physicians’ emotional experiences in response to COVID-19 and the coping strategies that they employed to navigate the pandemic. Methods From September 2020 to February 2021, we conducted semistructured interviews with 26 emergency physicians recruited from 2 early COVID-19 epicenters: New York City and the Metro Boston region. Interviews, coding, and analyses were conducted using a grounded theory approach. Results Emergency physicians reported heightened anxiety, empathy, sadness, frustration, and anger during the pandemic. Physicians frequently attributed feelings of anxiety to medical uncertainty around the COVID-19 virus, personal risk of contracting the virus and transmitting it to family members, the emergency environment, and resource availability. Emergency physicians also discussed the emotional effects of policies prohibiting patients’ family members from entering the emergency department (ED), both on themselves and patients. Sources of physician anger and frustration included changing policies and rules, hospital leadership and administration, and pay cuts. Some physicians described an evolving, ongoing coping process in response to the pandemic, and most identified collective discussion and processing within the emergency medicine community as an effective coping strategy. Conclusions Our findings underscore the need to investigate the effects of physicians’ pandemic-related emotional stress and burnout on patient care. Evidence-based interventions to support emergency physicians in coping with pandemic-related trauma are needed

Effects of time window size and placement on the structure of aggregated networks

Complex networks are often constructed by aggregating empirical data over time, such that a link represents the existence of interactions between the endpoint nodes and the link weight represents the intensity of such interactions within the aggregation time window. The resulting networks are then often considered static. More often than not, the aggregation time window is dictated by the availability of data, and the effects of its length on the resulting networks are rarely considered. Here, we address this question by studying the structural features of networks emerging from aggregating empirical data over different time intervals, focussing on networks derived from time-stamped, anonymized mobile telephone call records. Our results show that short aggregation intervals yield networks where strong links associated with dense clusters dominate; the seeds of such clusters or communities become already visible for intervals of around one week. The degree and weight distributions are seen to become stationary around a few days and a few weeks, respectively. An aggregation interval of around 30 days results in the stablest similar networks when consecutive windows are compared. For longer intervals, the effects of weak or random links become increasingly stronger, and the average degree of the network keeps growing even for intervals up to 180 days. The placement of the time window is also seen to affect the outcome: for short windows, different behavioural patterns play a role during weekends and weekdays, and for longer windows it is seen that networks aggregated during holiday periods are significantly different.Comment: 19 pages, 11 figure

A Case of Diabetic Ketoacidosis Presenting with Hypernatremia, Hyperosmolarity, and Altered Sensorium

Diabetic Ketoacidosis commonly presents with hyponatremia, but hypernatremia is a rare entity. We report a unique case of a 50-year-old woman admitted with altered sensorium with blood glucose 979 milligrams/deciliter, serum osmolarity 363 mOsm/kilograms, and serum sodium 144 milliequivalents/liter. Patient was given initial bolus of isotonic saline and continued on half isotonic saline for correction of hypernatremia along with insulin infusion therapy. Patient was successfully treated with intravenous fluids, insulin infusion, and the altered sensorium was resolved without any sequelae. This case illustrates a teaching point in the use of intravenous fluids for the treatment of Diabetic Ketoacidosis with hypernatremia

ACQR: Acoustic Quick Response Codes for Content Sharing on Low End Phones with No Internet Connectivity.

ABSTRACT In this paper we introduce Acoustic Quick Response codes to facilitate sharing between Interactive Voice Response (IVR) service users. IVRs are telephone-based, and similar to the world wide web in many aspects, but currently lack support for content sharing. Our approach uses &apos;audio codes&apos; to let people share their call positions, and allows callers to hold their normal (low-end) handsets together to synchronise. The technique uses remote generation and recognition of audio codes to ensure that sharing is possible on any type of phone without the need for textual literacy or an internet connection. We begin by exploring existing user needs for sharing, then evaluate the technical robustness of our audio-based design. We demonstrate the value of the approach for voice service users over several separate studies-including an eight-month extended field deployment-then conclude with a discussion of future possibilities for such scenarios