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Review of Paul Hamann-Rose, <i>Genetics and the Novel: Reimagining Life Through Fiction</i>
No full textMulti-dimensional oscillatory activity of mouse GnRH neurons in vivo
No full textThe gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH). The GnRH neuron dendrons also exhibited a low level of unchanging clustered, rapidly fluctuating baseline activity in males and throughout the estrous cycle in females. In female mice, a gradual increase in basal activity that exhibited ~80 min oscillations began in the afternoon of proestrus and lasted for 12 hr. This was associated with the onset of the LH surge that ended several hours before the fall in the GCaMP signal. Abrupt 8 min duration episodes of GCaMP activity continued to occur on top of the rising surge baseline before ceasing in estrus. These observations provide the first description of GnRH neuron activity in freely behaving animals. They demonstrate that three distinct patterns of oscillatory activity occur in GnRH neurons. These are comprised of low-level rapid baseline activity, abrupt 8 min duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and very prolonged oscillating increase in activity responsible for the preovulatory LH surge.</p
pegBits: Experimenting with a 0.1" system for open hardware prototyping
No full textIn this paper we introduce a work in progress prototyping system for constructing 3D prototypes to house open hardware electronics. The system, called pegBits, takes the standardised 0.1” hole separation found in 2D perfboard and breadboards and extends it to a construction system in 3D. We describe our motivations for doing so that includes: making prototyping more accessible, taking a designerly and crafty approach to prototype design and searching for the elusive space between off-the-shelf and custom designed. We show our development and present a series of reflections on the ways we can make prototyping with open hardware more accessible to the communities of practice that we engage with
Association between medication adherence and cardiovascular outcomes in patients with both diabetes and hypertension in primary care settings in Canada:a retrospective cohort study
No full textObjectives The impact of concurrent adherence to antihypertensives, antidiabetics, and statins on cardiovascular disease (CVD) outcomes and intermediate clinical outcomes in people with hypertension and diabetes remains unclear. This study aimed to evaluate the association between medication adherence and CVD outcomes in such patients. Methods This retrospective cohort study analyzed the electronic medical records of 36,211 adults aged 18 or older diagnosed with hypertension and diabetes between January 2008 and June 2016 in Canada. Patients were prescribed antihypertensives, antidiabetics, and statins, with a minimum 1-year follow-up post-diagnosis. Medication adherence was determined by the proportion of days covered (PDC). For monotherapy, a PDC≥80% and <80% was reflected high and low adherence respectively. In multiple medication scenarios, adherence was considered high when each medication was at PDC≥80%; low when any medication fell below 80%. The primary outcome encompassed cardiac events, including coronary heart disease, stroke, and heart failure. Intermediate clinical outcomes included changes in diastolic blood pressure (DBP), Systolic Blood Pressure (SBP), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC). Cox regression models assessed the association between medication adherence and CVD morbidity, all-cause mortality, and intermediate clinical outcomes. Results High adherence to antidiabetic and statin monotherapy was associated with a lower all-cause mortality risk (aHR=0.67, P=0.001; aHR=0.68, P<0.001, respectively). For patients simultaneously prescribed three medications, higher adherence was linked to significant reductions in DBP (6 months: coefficient −0.52, P=0.01; 12 months: coefficient −0.44, P=0.02; 18 months: coefficient −0.55, P=0.004) and LDL-C (6 months: coefficient −0.04, P=0.02; 12 months: coefficient −0.05, P=0.01; 18 months: coefficient −0.04, P=0.02). Conclusions High adherence to antidiabetic and statin monotherapy correlated with lower all-cause mortality risk and improved intermediate clinical outcomes. However, simultaneous adherence to three medications did not significantly affect CVD outcomes, but influenced intermediate outcomes. Therefore, improving adherence to antihypertensives, antidiabetics, and statins among patients with hypertension and diabetes is important in primary care settings.</p
Bi-functional oxygen electrocatalysts for reversible solid oxide cells:the influence of A-site non-stoichiometry on the system (La or Ba)<sub>0.6–x</sub>Sr<sub>0.4</sub>Co<sub>0.8</sub>Fe<sub>0.2</sub>O<sub>3−δ</sub>
No full textSelective tailoring of stoichiometry in perovskite oxide generates excellent electrocatalytic activity toward redox reaction of oxygen [oxygen evolution reaction (OER) and oxygen reduction reaction (ORR)]. The redox reaction of oxygen is kinetically sluggish (spin relaxed reaction) and is the rate-limiting step for solid oxide cells (SOCs). We have reported that introducing non-stoichiometry at the A-site in A0.6–xSr0.4Co0.8Fe0.2O3−δ imparts a bifunctional electrocatalyst for OER and ORR with excellent performance in fuel cell (FC) and electrolyzer cell (EC) mode. Two compositions, Ba0.6Sr0.4Co0.8Fe0.2O3−δ (BSCF-6482) and La0.6Sr0.4Co0.8Fe0.2O3−δ (LSCF-6482), are designed by varying the non-stoichiometry from 0.6 to 0.52 for Ba and La, respectively. X-ray photoelectron spectroscopy (XP spectroscopy), iodometric estimation, and O2-temperature-programmed desorption (O2-TPD) reveal that Ba0.54Sr0.4Co0.8Fe0.2O3−δ (BS-54) promotes oxygen surface exchange (higher β-oxygen population) and La0.54Sr0.4Co0.8Fe0.2O3−δ (LS-54) accelerates α-oxygen desorption (charge-transfer reaction). A study of the distribution of relaxation time (DRT) using EIS (electrochemical impedance spectroscopy) on cell configuration LS-54 (or BS-54)/GDC-LS-54 (or BS-54)//GDC//Pt@800 °C reveals that LS-54 has minimum electrode polarization (comprising dual processes of charge transfer and oxygen surface exchange) at both +0.8 V (OER) and −0.8 V (ORR), which resonates at 103–104 Hz. It is corroborated that α-oxygen is associated with the charge-transfer process and controls the ORR, whereas the OER is assisted by oxygen surface exchange, primarily linked with β-oxygen. Inclusion of non-stoichiometry at the A-site promotes oxygen-vacancy formation and stabilizes a lower valence state for the B-site cations. The rate-controlling steps for the OER and ORR thereby alter in LS-54 and BS-54 compared to LSCF/BSCF-6482. Electrochemical measurements show superior reversible solid oxide cell (SOC) performance of LS-54 having a current density (CD) of 1.27 A cm–2 @1.5 V and 0.66 A cm–2 @0.5 V for a cell with dimensions as large as 5 cm × 5 cm. A similar cell operated with a CD of 1.0 A cm2 under standalone mode of operation in FC. This work proposes a novel strategy to demonstrate A-site non-stoichiometric La0.54Sr0.4Co0.8Fe0.2O3−δ to be a superior bifunctional electrocatalyst for both OER and ORR for SOCs
A punny fellow::the disconcerting wit of Thomas Hood
No full textReview of Thomas Hood by Peter Thorogoo
Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin
No full textConjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor–recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals. The reference IncHI1 plasmid R27, isolated from Salmonella enterica serovar Typhi, encodes the conjugative H-pilus subunit TrhA containing 74 residues after cleavage of the signal sequence. Here, we show that the H-pilus forms long filamentous structures that mediate MPF and describe its cryoelectron-microscopic (cryo-EM) structure at 2.2 Å resolution. Like the F pilus, the H-pilin subunits form helical assemblies with phospholipid molecules at a stoichiometric ratio of 1:1. While there were previous reports that the T-pilus from Agrobacterium tumefaciens was composed of cyclic subunits, three recent cryo-EM structures of the T-pilus found no such cyclization. Here, we report that the H-pilin is cyclic, with a covalent bond connecting the peptide backbone between the N and C termini. Both the cryo-EM map and mass spectrometry revealed cleavage of the last five residues of the pilin, followed by cyclization via condensation of the amine and carboxyl residues. Mutagenesis experiments revealed that loss of cyclization abolished pilus biogenesis and efficient plasmid transfer. The cyclic nature of the pilin could stabilize the pilus and may explain the high incidence of IncH plasmid dissemination
A viro-immunological model to characterize the antiviral effect of molnupiravir in SARS-CoV-2-infected outpatients:implication for treatment duration
No full textBackground: The antiviral efficacy of molnupiravir against SARS-CoV-2 is controversial. Here, we develop a model integrating viral and immune dynamics to characterize the mechanism of action of molnupiravir in vivo and its impact on viral dynamics, during and after treatment.Methods: We analysed data from the PANORAMIC trial, where 577 outpatients were randomised shortly after symptom onset to receive usual care or molnupiravir for 5 days, and where viral and immunological data were collected for two weeks. We developed a mathematical model that characterized virus/host interaction and accounted for the impact of molnupiravir on viral replication and mutagenesis. The model was used to explore the impact of longer treatment duration.Results: Molnupiravir reduced RNA replication with an efficacy that reached 93% at the end of a five-day treatment. This effect was mediated through two different pathways, one that increased transition mutation frequency, and other that directly inhibited viral production. Accordingly five-day treatment shortened the median time to clearance of both RNA and infectious virus by approximately 2 days. Treatment duration of 10 days could reduce the time to RNA clearance by 5 days and reduce the occurrence of viral rebounds. Longer treatment durations might be needed in case of post-exposure prophylaxis.Conclusions: Our model suggests that molnupiravir acts primarily on viral replication, and does not act specifically on viral infectivity. Longer administration of molnupiravir may reduce rebound rate and shorten time to viral clearance.</p
Dive-by-dive variation in the diving respiratory air volume of southern elephant seals (<i>Mirounga leonina</i>)
No full textThe role of diving respiratory air volume (DRAV) in deep-diving phocid seals remains poorly understood, largely because of the lack of methods for measuring DRAV in free-ranging divers that exhale before diving. We developed a method to estimate DRAV using a hydrodynamic glide model applied to descent glides recorded using multi-sensor data loggers. We estimated dive-by-dive DRAV for six negatively buoyant female southern elephant seals (Mirounga leonina). During shallow descent glides, rapid compression of DRAV influenced net buoyancy and gliding speed, making this phase suitable for estimating DRAV. Our results revealed dive-by-dive variation in DRAV, which was positively correlated with root mean square (RMS) sway acceleration (a proxy for per-stroke effort) and the depth at which gliding began during the initial descent. DRAV increased with both tissue density and maximum dive depth, suggesting that seals adjusted their DRAV to stay closer to neutral buoyancy through their dives. However, the observed level of adjustment did not result in neutral buoyancy at half of the maximum dive depth, as predicted to minimise round-trip locomotion costs. Instead, the seals typically adjusted DRAV to reach neutral buoyancy at ∼30 m depth, <10% of their mean maximum dive depth. This indicates that strong negative tissue density imposes transit costs that cannot be fully compensated for by DRAV adjustment alone. Future work should explore whether other breath-hold divers show similar patterns of DRAV adjustment and quantify the associated physiological and ecological benefits