Social threat alters the behavioral structure of social motivation and reshapes functional brain connectivity.

Traumatic social experiences redefine socially motivated behaviors to enhance safety and survival. Although many brain regions have been implicated in signaling a social threat, the mechanisms by which global neural networks regulate such motivated behaviors remain unclear. To address this issue, we first combined traditional and modern behavioral tracking techniques in mice to assess both approach and avoidance, as well as sub-second behavioral changes, during a social threat learning task. We were able to identify previously undescribed body and tail movements during social threat learning and recognition that demonstrate unique alterations into the behavioral structure of social motivation. We then utilized inter-regional correlation analysis of brain activity after a mouse recognizes a social threat to explore functional communication amongst brain regions implicated in social motivation. Broad brain activity changes were observed within the nucleus accumbens, the paraventricular thalamus, the ventromedial hypothalamus, and the nucleus of reuniens. Inter-regional correlation analysis revealed a reshaping of the functional connectivity across the brain when mice recognize a social threat. Altogether, these findings suggest that reshaping of functional brain connectivity may be necessary to alter the behavioral structure of social motivation when a social threat is encountered.

Synthesis of Structural ADP-Ribose Analogues as Inhibitors for SARS-CoV-2 Macrodomain 1.

Protein adenosine diphosphate (ADP)-ribosylation is crucial for a proper immune response. Accordingly, viruses have evolved ADP-ribosyl hydrolases to remove these modifications, a prominent example being the SARS-CoV-2 NSP3 macrodomain, "Mac1". Consequently, inhibitors are developed by testing large libraries of small molecule candidates, with considerable success. However, a relatively underexplored angle in design pertains to the synthesis of structural substrate mimics. Here, we present the synthesis and biophysical activity of novel adenosine diphosphate ribose (ADPr) analogues as SARS-CoV-2 NSP3 Mac1 inhibitors.

Heterologous SARS-CoV-2 booster vaccine for individuals with hematological malignancies after a primary SARS-CoV-2 mRNA vaccine series.

Heterologous COVID-19 vaccine boosters have not been evaluated for patients with hematological malignancies. A Novavax booster was administered for 56 individuals with hematological malignancies who had received a primary COVID-19 series and prior boosters with mRNA vaccines only. Blood specimens were obtained at baseline (pre-vaccine), 28 days, and 168 days after vaccination with the Novavax booster. The median fold change of anti-Spike IgG was 1.02 (IQR 0.79, 1.3) between baseline and Day 28. Circulating Spike protein-specific B cells increased 1.4-fold at Day 28 (p < 0.05). Increases in antibody and T cell responses were modest without significance, with a waning of humoral and cellular responses at 168 days after vaccination.

Early arrival of spring-spawning Atlantic herring Clupea harengus at their spawning ground in the Kiel Fjord, western Baltic, relates to increasing winter seawater temperature.

The disturbance of marine organism phenology due to climate change and the subsequent effects on recruitment success are still poorly understood, especially in migratory fish species, such as the Atlantic herring (Clupea harengus; Clupeidae). Here we used the commercial catch data from a local fisher over a 50-year period (1971-2020) to estimate western Baltic spring-spawning (WBSS) herring mean arrival time Q50 (i.e., the week when 50% of the total fish catches had been made) at their spawning ground within the Kiel Fjord, southwest Baltic Sea, and the duration of the spawning season for each year. The relationship between the seawater temperature in the Kiel Bight and other environmental parameters (such as water salinity, North Atlantic and Atlantic multidecadal oscillations) and Q50 was evaluated using a general linear model to test the hypothesis that fish arrived earlier after warm than cold winters. We also estimated the accumulated thermal time to Q50 during gonadal development to estimate the effects of seawater temperature on the variations of Q50. The results of this study revealed a dramatic decrease in herring catches within the Kiel Fjord since the mid-1990s, as documented for the whole southwestern Baltic Sea. Warmer winter seawater temperature was the only factor related to an earlier arrival (1 week for one January seawater temperature degree increase) of herring at their spawning ground. The relationship was found for the first time on week 52 of the year prior to spawning and was the strongest (50% of the variability explained) from the fourth week of January (8 weeks before the mean Q50 among the studied years). A thermal constant to Q50 (~316°C day) was found when temperatures were integrated from the 49th week of the year prior to spawning. These results indicate that seawater temperature enhanced the speed of gonadal maturation during the latest phases of gametogenesis, leading to an early fish arrival under warm conditions. The duration of the spawning season was elongated during warmer years, therefore potentially mitigating the effects of trophic mismatch when fish spawn early. The results of this study highlight the altering effects of climate change on the spawning activity of a migratory fish species in the Baltic Sea where fast global changes presage that in other coastal areas worldwide.

Non-destructive identification of varieties of Hawaii-grown avocados using near-infrared spectroscopy: Feasibility studies using bench-top and handheld spectrometers.

Avocados are an important economic crop of Hawaii, contributing to approximately 3% of all avocados grown in the United States. To export Hawaii-grown avocados, growers must follow strict United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) regulations. Currently, only the Sharwil variety can be exported relying on a systems approach, which allows fruit to be exported without quarantine treatment; treatments that can negatively impact the quality of avocados. However, for the systems approach to be applied, Hawaii avocado growers must positively identify the avocados variety as Sharwil with APHIS prior to export. Currently, variety identification relies on physical characteristics, which can be erroneous and subjective, and has been disputed by growers. Once the fruit is harvested, variety identification is difficult. While molecular markers can be used through DNA extraction from the skin, the process leaves the fruit unmarketable. This study evaluated the feasibility of using near-infrared spectroscopy to non-destructively discriminate between different Hawaii-grown avocado varieties, such as Sharwil, Beshore, and Yamagata, Nishikawa, and Greengold, and to positively identify Sharwil from the other varieties mentioned above. The classifiers built using a bench-top system achieved 95% total classification rates for both discriminating the varieties from one another and positively identifying Sharwil while the classifier built using a handheld spectrometer achieved 96% and 96.7% total classification rates for discriminating the varieties from one another and positively identifying Sharwil, respectively. Results from chemometric methods and chemical analysis suggested that water and lipid were key contributors to the performance of classifiers. The positive results demonstrate the feasibility of NIR spectroscopy for discriminating different avocado varieties as well as authenticating Sharwil. To develop robust and stable models for the growers, distributors, and regulators in Hawaii, more varieties and additional seasons should continue to be added.

Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation.

Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a 729 nm and a 1069 nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the 1069 nm coating. We show that the fractional frequency instability of the 729 nm laser is limited by RAM at 1 × 10-14. The instability of the 1069 nm laser is at 3 × 10-15 close to the thermal noise limit of 1.5 × 10-15.

Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

How much can performance measures explain of the between-cow variation in enteric methane?

Enteric CH4 produced from dairy cows contributes to the emission of greenhouse gases from anthropogenic sources. Recent studies have shown that the selection of lower CH4-emitting cows is possible, but doing so would be simpler if performance measures already recorded on farm could be used, instead of measuring gas emissions from individual cows. These performance measures could be used for selection of low emitting cows. The aim of this analysis was to quantify how much of the between-cow variation in CH4 production can be explained by variation in performance measures. A dataset with 3 experiments and a total of 149 lactating dairy cows with repeated measures was used to estimate the between-cow variation (the variation between cow estimates) for performance and gas measures from GreenFeed (C-Lock, Rapid City, SD). The cow estimates were obtained with a linear mixed model with the diet within period effect as a fixed effect and the cow within experiment as a random effect. The cow estimates for CH4 production were first regressed on the performance and gas measures individually, and then performance and CO2 production measures were grouped in 3 subsets for principal component analysis and principal component regression. The variables that explained most of the between-cow variation in CH4 production were DMI (R2 = 0.44), among the performance measures, and CO2 production (R2 = 0.61), among gas measures. Grouping the measures increased the R2 to 0.53 when only performance measures were used, and to 0.66 when CO2 production was added to the significant performance measures. We found the marginal improvement to be insufficient to justify the use of grouped measures rather than an individual measure because the latter simplifies the model and avoids over-fitting. Investigation of other measures that can be explored to increase explanatory power of between-cow variation in CH4 production is briefly discussed. Finally, the use of residual CH4 as a measure for CH4 efficiency could be considered by using either DMI or CO2 production as the sole predicting variables.

Harnessing noncanonical crRNAs to improve functionality of Cas12a orthologs.

There is a broad diversity among Cas12a endonucleases that possess nucleic acid detection and gene-editing capabilities, but few are studied extensively. Here, we present an exhaustive investigation of 23 Cas12a orthologs, with a focus on their cis- and trans-cleavage activities in combination with noncanonical crRNAs. Through biochemical assays, we observe that some noncanonical crRNA:Cas12a effector complexes outperform their corresponding wild-type crRNA:Cas12a. Cas12a can recruit crRNA with modifications such as loop extensions and split scaffolds. Moreover, the tolerance of Cas12a to noncanonical crRNA is also observed in mammalian cells through the formation of indels. We apply the adaptability of Cas12a:crRNA complexes to detect SARS-CoV-2 in clinical nasopharyngeal swabs, saliva samples, and tracheal aspirates. Our findings further expand the toolbox for next-generation CRISPR-based diagnostics and gene editing.

Evidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas.

Insulin dysregulation in horses is characterised by hyperinsulinaemia and/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas. Tissue samples were collected from the stomach, small and large intestines, and pancreas of six mature horses following euthanasia. Samples of stomach contents and faeces were also collected. Immunohistochemistry was performed to identify tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine production, and dopamine D2 receptors in tissue sections. Additional immunostaining for glucagon, insulin and chromogranin A was performed to identify α cells, ß cells and enteroendocrine cells, respectively. Gastric parietal cells expressed both TH and D2 receptors, indicating that they are capable of both producing and responding to dopamine. Dopamine was quantified in stomach contents and faeces by high-performance liquid chromatography with electrochemical detection, with similar concentrations found at both sites. Dopamine D2 receptors were expressed in duodenal epithelial cells but not more distally. A subset of enteroendocrine cells, located sporadically along the gastrointestinal tract, were found to be immunopositive for the D2 receptor. In pancreatic islets, TH was present in α cells, while D2 receptors were strongly expressed in ß cells and variably expressed in α cells. These findings are consistent with studies of other species; however, dynamic studies are required to further elucidate the role of dopamine in the modulation of insulin and glucagon secretion in horses. This descriptive study provides preliminary evidence for a potential role of dopamine to act as a paracrine messenger in the gastrointestinal mucosa and endocrine pancreas of horses.

When another one bites the dust: Environmental impact of global copper demand on local communities in the Atacama mining hotspot as registered by tree rings.

Assessing the impact of mining activity on the availability of environmental pollutants is crucial for informing health policies in anticipation of future production scenarios of critical minerals essential for the transition to a net-zero carbon society. However, temporal and spatial monitoring is often sparse, and measurements may not extend far enough back in time. In this study, we utilize variations of chemical elements contained in tree-rings collected in local villages from an area heavily affected by copper mining in the Atacama Desert since the early 20th century to evaluate the temporal distribution of pollutants and their relationship with local drivers. By combining time-varying data on local drivers, such as copper production and the dry tailings deposit area, we show how the surge in copper production during the 1990s, fueled by trade liberalization and increased international demand, led to a significant increment in the availability of metal(loid)s related to mining activities on indigenous lands. Our findings suggest that the environmental legislation in Chile may be underestimating the environmental impact of tailing dams in neighboring populations, affecting the well-being of Indigenous Peoples from the Atacama mining hotspot region. We argue that future changes in production rates driven by international demand could have negative repercussions on the environment and local communities. Therefore, mining emissions and the management of tailing dams should be carefully considered to anticipate their potential negative effects on human and ecosystem health.

Clinical Characteristics of Idiopathic Intracranial Hypertension in Older Adults.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition that classically affects obese women of child-bearing age. However, it is sometimes encountered in older patients. The purpose of this study was to help clinicians better understand how this disease can present differently in these age groups. METHODS: This is a retrospective chart review from a single academic center of baseline characteristics of adult patients diagnosed with IIH based on the modified Dandy criteria. The patients were divided into 2 groups: (1) those 18-44 years old and (2) those older than 45 years at diagnosis. RESULTS: One hundred sixty-seven patients were identified; 135 in the younger group and 32 in the older group. The younger group had a higher rate of headaches (90% vs 63%, P = 0.0004), higher body mass index (38.9 vs 36.1, P = 0.046), higher opening pressure (38 vs 31 cm H2O, P = 0.005), and thicker peripapillary retinal nerve fiber layer average thickness (right eye 178 vs 131 µm, P = 0.02; left eye 184 vs 136 µm, P = 0.045). The older group had higher rates of empty sella (90% vs 62%, P = 0.0039). In addition in the younger group, there was a trend toward higher rates of pulsatile tinnitus (63% vs 45%, P = 0.08), transient visual obscurations (50% vs 32%, P = 0.07), and lower rates of spontaneous cerebrospinal fluid leak (4% vs 13%, P = 0.08). Sex, rates of obesity, other MRI findings typical of elevated intracranial pressure, frequency and Frisen grading of papilledema, and visual field loss were not statistically different between the groups. CONCLUSIONS: The older age group had milder signs and symptoms of IIH and a higher prevalence of empty sella than the younger group, but otherwise had typical characteristics. These findings suggest that IIH in the older age group may represent milder chronic disease that was previously undiagnosed.

Developmental Neuroendocrinology of Early-Life Stress: Impact on Child Development and Behavior.

Our internal balance, or homeostasis, is threatened or perceived as threatened by stressful stimuli, the stressors. The stress system is a highly conserved system that adjusts homeostasis to the resting state. Through the concurrent activation of the hypothalamic-pituitary-adrenal axis and the locus coeruleus/norepinephrine-autonomic nervous systems, the stress system provides the appropriate physical and behavioral responses, collectively termed as "stress response", to restore homeostasis. If the stress response is prolonged, excessive or even inadequate, several acute or chronic stress-related pathologic conditions may develop in childhood, adolescence and adult life. On the other hand, earlylife exposure to stressors has been recognized as a major contributing factor underlying the pathogenesis of non-communicable disorders, including neurodevelopmental disorders. Accumulating evidence suggests that early-life stress has been associated with an increased risk for attention deficit hyperactivity disorder and autism spectrum disorder in the offspring, although findings are still controversial. Nevertheless, at the molecular level, early-life stressors alter the chemical structure of cytosines located in the regulatory regions of genes, mostly through the addition of methyl groups. These epigenetic modifications result in the suppression of gene expression without changing the DNA sequence. In addition to DNA methylation, several lines of evidence support the role of non-coding RNAs in the evolving field of epigenetics. In this review article, we present the anatomical and functional components of the stress system, discuss the proper, in terms of quality and quantity, stress response, and provide an update on the impact of early-life stress on child development and behavior.

The influence of risk awareness and government trust on risk perception and preparedness for natural hazards.

Risk perception is considered the primary motivator for taking preparedness actions. But people with prior experience and a high-risk perception are not necessarily more prepared. This relationship is even more complex when assessing preparedness levels for hazards with different characteristics. These inconsistent findings can be explained by how preparedness has been measured and the influence of other factors, such as trust and risk awareness. Thus, the main goal of this study was to analyze the role of risk awareness and trust in authorities on risk perception and intention to prepare for natural hazards in a coastal city in Chile. A representative sample of the city of Concepción, located in the center-south zone of Chile (n = 585), completed a survey. We measured risk awareness, risk perception, trust in authorities, and intention to prepare for two hazards: earthquakes/tsunamis and floods. Through structural equation models, we tested five hypotheses. We found that the perception of risk maintained a direct and positive influence on the intention to prepare for both hazards. The results showed that awareness and risk perception influence the intention to prepare and should be considered different concepts. Finally, trust did not significantly influence risk perception when faced with known hazards for the population. Implications for understanding the relationship between risk perception and direct experience are discussed.

Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft.

Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs), including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD), were assessed from day 0 through day +365. The 1-year cumulative incidence functions of OIs and nonrelapse mortality (NRM) were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% for haploidentical versus 25% for MUD/MMUD; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.16 to 2.49; P = .006). On multivariable analysis, haploidentical donor (HR, 1.50; 95% CI, 1.01 to 2.23; P = .046), prior HCT (HR, 1.99; 95% CI, 1.29 to 3.09; P = .002), and diagnosis of aGVHD (HR, 1.47; 95% CI, 1.02 to 2.14; P = .041) were associated with increased risk of OIs. NRM within the first year was not significantly different between the 2 cohorts (HR, 1.11; 95% CI, .64 to 1.93; P = .70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although 1-year NRM was not different between haploidentical HCT and MUD/MMUD HCT recipients. CMV and AdV infections were significantly increased among haploidentical HCT recipients, whereas the incidences of EBV infection and IFD were similar in the 2 cohorts. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.

Correction: Balaphas et al. Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand? Cells 2021, 10, 2086.

The authors would like to add a new reference to the section "3 [...].

Long-Term Outcome and Complications of IOL-Exchange.

Purpose: To describe the long-term outcome after intraocular lens (IOL) exchange for IOL-opacification with a focus on any occurring complications. Patients and Methods: Patients with an IOL exchange for opacified IOLs (Lentis LS-502-1) were identified. Medical records and information from the treating ophthalmologists were reviewed. Visual outcomes and any occurring complications after the IOL exchange were analyzed. Results: IOL exchange was performed in 48 eyes of 46 patients and significantly improved best-corrected distance visual acuity from 0.42 ± 0.32 logMar (mean ± SD) in opacified lenses to 0.25 ± 0.28 logMar after IOL exchange. Nine of the 48 eyes (19%) underwent 11 further surgical procedures for complications due to four indications: IOL dislocation (n = 2, 4%), retinal detachment (RD) (n = 6, 12%), epiretinal membrane (n = 2, 4%), and pupillary block (n = 1, 2%). Three eyes (6%) developed a temporarily elevated intraocular pressure. Temporary postoperative cystoid macular edema was found in 2 eyes (4%). Conclusion: IOL exchange can restore vision owing to IOL opacification in most cases. Nonetheless, IOL exchange is not an easy or risk-free procedure. This may lead to sight-threatening complications, even in eyes without predisposing ocular comorbidities.

Efficient Concatenated Bosonic Code for Additive Gaussian Noise.

Bosonic codes offer noise resilience for quantum information processing. Good performance often comes at a price of complex decoding schemes, limiting their practicality. Here, we propose using a Gottesman-Kitaev-Preskill code to detect and discard error-prone qubits, concatenated with a quantum parity code to handle the residual errors. Our method employs a simple linear-time decoder that nevertheless offers significant performance improvements over the standard decoder. Our Letter may have applications in a wide range of quantum computation and communication scenarios.