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Temperature is a fundamental sensory modality separate from touch, with dedicated receptor channels and primary afferent neurons for cool and warm 1 – 3 . Unlike for other modalities, however, the cortical encoding of temperature remains unknown, with very few cortical neurons reported that respond to non-painful temperature, and the presence of a ‘thermal cortex’ is debated 4 – 8 . Here, using widefield and two-photon calcium imaging in the mouse forepaw system, we identify cortical neurons that respond to cooling and/or warming with distinct spatial and temporal response properties. We observed a representation of cool, but not warm, in the primary somatosensory cortex, but cool and warm in the posterior insular cortex (pIC). The representation of thermal information in pIC is robust and somatotopically arranged, and reversible manipulations show a profound impact on thermal perception. Despite being positioned along the same one-dimensional sensory axis, the encoding of cool and that of warm are distinct, both in highly and broadly tuned neurons. Together, our results show that pIC contains the primary cortical representation of skin temperature and may help explain how the thermal system generates sensations of cool and warm. A study using calcium imaging in the mouse forepaw system identifies neurons in the posterior insular cortex that respond to cooling and/or warming with distinct response dynamics.

We present 1.8 yr of near-daily Swift monitoring of the bright, strongly variable Type 1 active galactic nucleus (AGN) Fairall 9. Totaling 575 successful visits, this is the largest such campaign reported to date. Variations within the UV/optical are well correlated, with longer wavelengths lagging shorter wavelengths in the direction predicted by thin-disk/lamppost models. The correlations are improved by “detrending,” subtracting a second-order polynomial fit to the UV/optical light curves to remove long-term trends that are not of interest to this study. Extensive testing indicates detrending with higher-order polynomials removes too much intrinsic variability signal on reverberation timescales. These data provide the clearest detection to date of interband lags within the UV, indicating that neither emission from a large disk nor diffuse continuum emission from the broad-line region (BLR) can independently explain the full observed lag spectrum. The observed X-ray flux variations are poorly correlated with those in the UV/optical. Further, subdivision of the data into four ∼160 days light curves shows that the UV/optical lag spectrum is highly stable throughout the four periods, but the X-ray to UV lags are unstable, significantly changing magnitude and even direction from one period to the next. This indicates the X-ray to UV relationship is more complex than predicted by the simple reprocessing model often adopted for AGN. A “bowl” model (lamppost irradiation and blackbody reprocessing on a disk with a steep rim) fit suggests the disk thickens at a distance (∼10 lt-day) and temperature (∼8000 K) consistent with the inner edge of the BLR.

Understanding how super-massive black holes form and grow in the early Universe has become a major challenge 1 , 2 since it was discovered that luminous quasars existed only 700 million years after the Big Bang 3 , 4 . Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust 5 . Although the last phase has been identified out to a redshift of 7.6 (ref. 6 ), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations 7 and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs. An unusual ultraviolet compact object associated with a dusty starburst has been observed at a redshift of about 7.2, with a luminosity that falls between that of quasars and galaxies, possibly in transition between the two. 

Copper has been used as an antimicrobial agent for over a century and is now being added to commercial fungicides. Nanomaterials have attracted much attention due to the special properties they have over their bulk form. We studied nanostructured copper (Cu-NPs), investigating the potential for improved antifungal properties derived from its special properties and studied any effect that the oxidation of copper (CuO-NPs) may have. We conducted this research against Colletotrichum gloeoesporioides, a devastating pathogen to plants/crops worldwide. Research on the effects of copper on this fungus are limited. Our studies showed that nanoforms of copper had significant antifungal activities, with Cu-NPs offering the most sustainable efficacy and was more effective than its oxidative form (CuO-NPs). Scanning Electron Microscopy (SEM) images of the treated pathogen show that the hyphae had a swollen appearance, lost their filamentous structure, and the mycelia had a powder-like structure, indicating the probable destruction of the hyphal tubular cell wall. X-ray Difractogram (XRD) outputs showed substantial changes in the physical characteristics of the Cu-NPs after interaction with the fungus. This is the first report to demonstrate chemo-physical changes in the metal compounds, opening new insights for further studies on the mechanism of copper’s antifungal properties.

We present new Chandra/ACIS-S imaging spectroscopy of two luminous type 2 quasars (QSO2s), FIRST J120041.4+314745 (z = 0.116) and 2MASX J13003807+5454367 (z = 0.088), and compare their X-ray emission with Hubble Space Telescope [O III]λ5007 morphologies and kinematics. Both systems show kiloparsec-scale soft X-ray emission. In FIRST J120041, the X-ray morphology is clumpy and closely follows the [O III] structures, with surface-brightness peaks cospatial with the highest [O III] velocities (600–750 km s−1) and broadest line widths (∼1700 km s−1). In 2MASX J130038, the X-ray emission is centrally concentrated and weakly correlated with rotational [O III] kinematics. Spectral modeling indicates that photoionization dominates the soft X-rays in both quasars. The inferred hot-gas reservoirs are substantial, MXray ∼ 4.5 × 108 M⊙ (FIRST J120041) and MXray ∼ 1.8 × 108 M⊙ (2MASX J130038), exceeding the outflowing [O III] masses by factors of ∼4 and ∼16. In 2MASX J130038, we identify a tentative blueshifted Fe XXVI Lyα line at Erest = 7.14 ± 0.06 keV (v ∼ 7600 km s−1), consistent with a hot wind confined to the inner few hundred parsecs. Combining these results with a broader sample of 12 QSO2s, we argue that luminous quasars evolve along a continuous feedback sequence regulated by progressive clearing of circumnuclear gas. As active galactic nucleus radiation and winds pierce the surrounding medium, systems transition from heavily enshrouded, compact configurations to phases where the X-ray and [O III] components strongly couple and, eventually, to energetically dominant outflows. FIRST J120041 and 2MASX J130038 represent two points along this sequence, tracing the emergence and growth of hot winds as primary drivers of quasar-scale feedback.

Background Chaperones play an important role in maintaining cellular proteostasis by mediating protein folding. As a result, chaperone overexpression has been widely used as a tool for enhancing folding and improving production of heterologous proteins in host organisms such as Saccharomyces cerevisiae . In contrast, this strategy has been much less explored for small molecule (SM) production. This is surprising, as SM pathways typically depend on multiple enzymes including large multi-domain synthases or synthetases, which may all benefit from folding assistance to enhance the catalytic power of the pathway. Results We have established an S. cerevisiae strain library of 68 strains overexpressing endogenous cytosolic chaperones and a mating-based method that allows the chaperone library to be combined with a query strain that contains the pathway of a desirable SM. Using the small molecule aspulvinone E from Aspergillus terreus as a model compound, we screened the chaperone library for chaperones that improve production of aspulvinone E. Screening of the library identified several chaperones and chaperone combinations that improved aspulvinone E production. Specifically, the combined overexpression of YDJ1 and SSA1 was identified as the best hit in our screen. Subsequently, we demonstrated that overexpression of YDJ1 and SSA1 improved aspulvinone E production by 84% in 1.5 mL scale batch fermentations. The observed increase is likely due to higher levels of the MelA synthetase responsible for aspulvinone E synthesis, as overexpression of YDJ1 and SSA1 increases the amounts of fluorescent MelA-mRFP in cells producing this fusion protein. Conclusion The endogenous cytosolic chaperone overexpression library and mating based screening method presented in this report constitute a tool allowing for fast and efficient identification of specific chaperones and chaperone combinations that benefit production of a given SM in S. cerevisiae -based cell factories.

This paper reviews the effects of extended lactation (EXT) as a strategy in dairy cattle on milk production and persistency, reproduction, milk quality, lifetime performance of the cow and finally the economic effects on herd and farm levels as well as the impact on emission of greenhouse gas at product level. Primiparous cows are able to produce equal or more milk per feeding day during EXT compared with a standard 305-d lactation, whereas results for multiparous cows are inconsistent. Cows managed for EXT can achieve a higher lifetime production while delivering milk with unchanged or improved quality properties. Delaying insemination enhances mounting behaviour and allows insemination after the cow’s energy balance has become positive. However, in most cases EXT has no effect or a non-significant positive effect on reproduction. The EXT strategy sets off a cascade of effects at herd and farm level. Thus, the EXT strategy leads to fewer calvings and thereby expected fewer diseases, fewer replacement heifers and fewer dry days per cow per year. The optimal lifetime scenario for milk production was modelled to be an EXT of 16 months for first parity cows followed by an EXT of 10 months for later lactations. Modelling studies of herd dynamics indicate a positive effect of EXT on lifetime efficiency (milk per dry matter intake), mainly originating from benefits of EXT on daily milk yield in primiparous cows and the reduced number of replacement heifers. Consequently, EXT also leads to reduced total meat production at herd level. For the farmer, EXT can give the same economic return as a traditional lactation period. At farm level, EXT can contribute to a reduction in the environmental impact of dairy production, mainly as a consequence of the reduced production of beef. A wider dissemination of the EXT concept will be supported by methods to predict which cows may be most suitable for EXT, and clarification of how milking frequency and feeding strategy through the lactation can be organised to support milk yield and an appropriate body condition at the next calving.

Early and quick detection of pathogens are crucial for managing the spread of infections in the biomedical, biosafety, food, and agricultural fields. While molecular diagnostics can offer the specificity and reliability in acute infectious diseases, detection of pathogens is often slowed down by the current benchtop molecular diagnoses, which are time consuming, labor intensive, and lack the mobility for application at the point-of-need. In this work, we developed a complete on-farm use detection protocol for the plant-devastating anthracnose agent: Colletotrichum gloeosporioides. Our methods combined a simplified DNA extraction on paper that is compatible with loop-mediated isothermal amplification (LAMP), coupled with paper-based immunoassay lateral flow sensing. Our results offer simple, quick, easy, and a minimally instrumented toolkit for Colletotrichum gloeosporioides detection. This scalable and adaptable platform is a valuable alternative to traditional sensing systems towards on-the-go pathogen detection in food and agriculture, biomedical, and other fields.

Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a 'natural' experiment using spousal bereavement as a disease-independent mental stressor. We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997-2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors. In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37-2.63; aHR, 6-12 months: 1.38, 95% CI 1.34-1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes. Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality.

Aim The aim was to assess safety and feasibility of Hybrid High-Intensity Interval Training (HIIT) using Functional Electrical Stimulation (FES) leg cycling and arm ski ergometer in people with Spinal Cord Injuries (SCI). Method Eight outpatients (mean age 42.8 years; 7 men) with stable SCI paraplegia (mean 14.5 years since injury) participated in hybrid HIIT (90% peak watts; 4 × 4–min intervals), three times a week (over 8 weeks). Primary outcomes were Adverse Events (AE), participant acceptability, shoulder pain, training intensity (% peak watts), and attendance. Secondary outcomes were effect on peak oxygen uptake (VO 2 peak) during FES hybrid poling, mean watts, self-reported leisure time physical activity, quality of life, and fatigue. Results No serious AE occurred; acceptability with the training modality was high, while shoulder pain increased by 9% ( SD 95.2). During training, 50% of the participants reached > 90% peak watts during the intervals, three with the legs (FES cycle) and one with the arms (Ski-Erg). Overall, mean training intensity (% peak watts) was 92% ( SD 18.9) for legs and 82% ( SD 10.3) for arms. Proportion of fulfilled training minutes was 82% (range 36–100%); one participant dropped out after 6 weeks due to back pain. Mean VO 2 peak increased by 17% ( SD 17.5). Participants reported increased leisure time physical activity and health-related quality of life, besides reduced fatigue. Conclusion Hybrid HIIT was safe for people with SCI paraplegia. The majority of the criteria for feasibility were met with acceptable attendance rate, limited drop out, participants enjoyed training, and increased VO 2 peak and mean watts. However, the intensity of 90% peak watts was reached by < 60% of the participants despite high RPE ratings during training. The method of measuring and calculating intensity needs to be studied further before a study using this HIIT protocol is undertaken. Trial registration Clinicaltrials.gov , NCT04211311 , registered 12 December 2019 retrospectively registered