Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we ...present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.
Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. There is growing recognition that food motivation is altered in people with ...obesity. However, it remains unclear how brain circuits that control food motivation are altered in obese animals.
Using a novel behavioral assay that quantifies work during food seeking, in vivo and ex vivo cell-specific recordings, and a synaptic blocking technique, we tested the hypothesis that activity of circuits promoting appetitive behavior in the core of the nucleus accumbens (NAc) is enhanced in the obese state, particularly during food seeking.
We first confirmed that mice made obese with ad libitum exposure to a high fat diet work harder than lean mice to obtain food, consistent with an increase in food motivation in obese mice. We observed greater activation of D
receptor-expressing NAc spiny projection neurons (NAc D1
) during food seeking in obese mice relative to lean mice. This enhanced activity was not observed in D
receptor-expressing neurons (D2
). Consistent with these in vivo findings, both intrinsic excitability and excitatory drive onto D1
were enhanced in obese mice relative to lean mice, and these measures were selective for D1
. Finally, blocking synaptic transmission from D1
, but not D2
, in the NAc core decreased physical work during food seeking and, critically, attenuated high fat diet-induced weight gain.
These experiments demonstrate the necessity of NAc core D1
in food motivation and the development of diet-induced obesity, establishing these neurons as a potential therapeutic target for preventing obesity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Carbon-donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5-1.0kcalmol-1) that are difficult to detect, and thus their roles in the structure and functionality of chemical systems ...often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second-order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing alphaHelix3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of alphaHelix3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of alphaHelix3 observed from experiment. A strongly correlated motion between alphaHelix3 and alphaHelices2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just alphaHelix3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena. PUBLICATION ABSTRACT
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A search for a standard-model-like Higgs boson in the H→WW and H→ZZ decay channels is reported, for Higgs boson masses in the range 145<
m
H
<1000 GeV. The search is based upon proton–proton ...collision data samples corresponding to an integrated luminosity of up to 5.1 fb
−1
at
and up to 5.3 fb
−1
at
, recorded by the CMS experiment at the LHC. The combined upper limits at 95 % confidence level on products of the cross section and branching fractions exclude a standard-model-like Higgs boson in the range 145<
m
H
<710 GeV, thus extending the mass region excluded by CMS from 127–600 GeV up to 710 GeV.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or ...interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation. Methods: 210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge). Findings: 16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p < 0.001). Patients who consumed cannabis had higher rates of psychiatric comorbidities (25.3 versus 16.8%; p < 0.001) and concomitant non-tobacco substance abuse (30.2 versus 7.0%; p < 0.001). Compared to non-users, patients with a diagnosis of cannabis use disorder had higher odds of requiring advanced post-procedural healthcare utilisation after adjusting for patient characteristics, concomitant substance use and socioeconomic factors (aOR adjusted odds ratio 1.16; 95% CI 1.02–1.32). By contrast, patients with ongoing non-medical cannabis use had lower odds of advanced post-procedural healthcare utilisation (aOR 0.87; 95% CI 0.81–0.92, compared to non-users). Interpretation: One in seven patients undergoing surgery or interventional procedures in 2020 reported cannabis consumption. Differential effects on post-procedural healthcare utilisation were observed between patients with non-medical cannabis use and cannabis use disorder. Funding: This work was supported by an unrestricted philantropic grant from Jeff and Judy Buzen to Maximilian S. Schaefer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hazardous work zones (i.e., hot, warm, and cold) are typically established by emergency response teams during hazardous materials (HAZMAT) calls but less consistently for fire responses to segment ...personnel and response activities in the immediate geographic area around the fire. Despite national guidelines, studies have documented the inconsistent use of respiratory protective equipment by firefighters at the fire scene. In this case-series report, we describe warm zone gas levels using multigas detectors across five independent fire incident responses all occurring in a large South Florida fire department. Multigas detector data collected at each fire response indicate the presence of sustained levels of volatile organic compounds in the "warm zone" of each fire event. These cases suggest that firefighters should not only implement strategies for multigas detector use within the warm zone but also include respiratory protection to provide adequate safety from toxic exposures in the warm zone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Carbon-donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5-1.0kcalmol super(-1)) that are difficult to detect, and thus their roles in the structure and functionality of chemical ...systems often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second-order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing alphaHelix3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of alphaHelix3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of alphaHelix3 observed from experiment. A strongly correlated motion between alphaHelix3 and alphaHelices2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just alphaHelix3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena. Don't forget about me! A lesser recognized form of hydrogen bonding in which carbon assumes the role of the donor atom has been identified in the medically significant protein Streptococcus pneumoniae hyaluronate lyase. Utilizing a computational approach, it is shown that this unique hydrogen bond cooperates with neighboring hydrogen bonds to lend the parent helix appreciable stability and flexibility (see figure).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Purpose: We performed this analysis of possible first night effects (FNEs) on sleep and respiratory parameters in order to evaluate the need for two serial night polysomnograms (PSGs) to ...diagnose obstructive sleep apnea (OSA) in epilepsy patients.
Methods: As part of a pilot multicenter clinical trial investigating the effects of treating sleep apnea in epilepsy, two nights of PSG recording were performed for 40 patients with refractory epilepsy and OSA symptoms. Sleep architecture was examined in detail, along with respiratory parameters including apnea/hypopnea index (AHI) and minimum oxygen saturation. Analysis included two‐tailed t‐tests, Wilcox sign rank analysis, and Bland Altman measures of agreement.
Results: Total sleep time differed between the two nights (night 1,363.8 min + 59.4 vs. 386.3 min + 68.6, p = 0.05). Rapid eye movement (REM) sleep and percentage of REM sleep were increased during night two (night 1: 12.3% + 5.9 vs. night 2: 15.5% + 6.2, p = 0.007), and the total minutes of slow‐wave sleep (SWS) were increased (night 1: 35.6 + 60.7 vs. night 2: 46.4 + 68.1, p = 0.01). No other sleep or respiratory variables differed between the two nights. Given an AHI inclusion criterion of five apneas per hour, the first PSG identified all but one patient with OSA.
Discussion: Respiratory parameters showed little variability between the first and second nights. Sleep architecture was mildly different between the first and second PSG night. Performing two consecutive baseline PSGs to diagnose OSA may not be routinely necessary in this population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model ...expectation is observed using a data sample collected in proton-proton collisions at √s=7 TeV corresponding to an integrated luminosity of 2.2 fb(-1). In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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