The complex relationship between disease resistance and yield in crops.

In plants, growth and defence are controlled by many molecular pathways that are antagonistic to one another. This results in a 'growth-defence trade-off', where plants temporarily reduce growth in response to pests or diseases. Due to this antagonism, genetic variants that improve resistance often reduce growth and vice versa. Therefore, in natural populations, the most disease resistant individuals are often the slowest growing. In crops, slow growth may translate into a yield penalty, but resistance is essential for protecting yield in the presence of disease. Therefore, plant breeders must balance these traits to ensure optimal yield potential and yield stability. In crops, both qualitative and quantitative disease resistance are often linked with genetic variants that cause yield penalties, but this is not always the case. Furthermore, both crop yield and disease resistance are complex traits influenced by many aspects of the plant's physiology, morphology and environment, and the relationship between the molecular growth-defence trade-off and disease resistance-yield antagonism is not well-understood. In this article, we highlight research from the last 2 years on the molecular mechanistic basis of the antagonism between defence and growth. We then discuss the interaction between disease resistance and crop yield from a breeding perspective, outlining the complexity and nuances of this relationship and where research can aid practical methods for simultaneous improvement of yield potential and disease resistance.

Oligo-barcode illuminates holocentric karyotype evolution in Rhynchospora (Cyperaceae).

Holocentric karyotypes are assumed to rapidly evolve through chromosome fusions and fissions due to the diffuse nature of their centromeres. Here, we took advantage of the recent availability of a chromosome-scale reference genome for Rhynchospora breviuscula, a model species of this holocentric genus, and developed the first set of oligo-based barcode probes for a holocentric plant. These probes were applied to 13 additional species of the genus, aiming to investigate the evolutionary dynamics driving the karyotype evolution in Rhynchospora. The two sets of probes were composed of 27,392 (green) and 23,968 (magenta) oligonucleotides (45-nt long), and generated 15 distinct FISH signals as a unique barcode pattern for the identification of all five chromosome pairs of the R. breviuscula karyotype. Oligo-FISH comparative analyzes revealed different types of rearrangements, such as fusions, fissions, putative inversions and translocations, as well as genomic duplications among the analyzed species. Two rounds of whole genome duplication (WGD) were demonstrated in R. pubera, but both analyzed accessions differed in the complex chain of events that gave rise to its large, structurally diploidized karyotypes with 2n = 10 or 12. Considering the phylogenetic relationships and divergence time of the species, the specificity and synteny of the probes were maintained up to species with a divergence time of ~25 My. However, karyotype divergence in more distant species hindered chromosome mapping and the inference of specific events. This barcoding system is a powerful tool to study chromosomal variations and genomic evolution in holocentric chromosomes of Rhynchospora species.

Resolving electron and hole transport properties in semiconductor materials by constant light-induced magneto transport.

The knowledge of minority and majority charge carrier properties enables controlling the performance of solar cells, transistors, detectors, sensors, and LEDs. Here, we developed the constant light induced magneto transport method which resolves electron and hole mobility, lifetime, diffusion coefficient and length, and quasi-Fermi level splitting. We demonstrate the implication of the constant light induced magneto transport for silicon and metal halide perovskite films. We resolve the transport properties of electrons and holes predicting the material's effectiveness for solar cell application without making the full device. The accessibility of fourteen material parameters paves the way for in-depth exploration of causal mechanisms limiting the efficiency and functionality of material structures. To demonstrate broad applicability, we further characterized twelve materials with drift mobilities spanning from 10-3 to 103 cm2V-1s-1 and lifetimes varying between 10-9 and 10-3 seconds. The universality of our method its potential to advance optoelectronic devices in various technological fields.

Closed Suction Drainage after Total Knee Arthroplasty with Concomitant Intravenous Tranexamic Acid Administration.

Drain use in total knee arthroplasty (TKA) remains controversial. Use has been associated with increased complications, particularly postoperative transfusion, infection, increased cost, and longer hospital stays. However, studies examining drain use were performed before widespread adoption of tranexamic acid (TXA), which markedly reduces transfusion without increasing venous thromboembolism events. We aim to investigate incidence of postoperative transfusion and 90-day return to the operating room (ROR) for hemarthrosis in TKA with use of drains and concomitant intravenous (IV) TXA. Primary TKAs from a single institution were identified from August 2012 to December 2018. Inclusion criteria were primary TKA, age 18 years and over where use of TXA, drains, anticoagulant, and pre- and postsurgical hemoglobin (Hb) were documented during the patient's admission. Primary outcomes were 90-day ROR specifically for hemarthrosis and rate of postoperative transfusion. A total of 2,008 patients were included. Sixteen patients required ROR, three of which were due to hemarthrosis. Drain output was statistically higher in the ROR group (269.3 vs. 152.4 mL, p = 0.05). Five patients required transfusion within 14 days (0.25%). Patients requiring transfusion had significantly lower presurgical Hb (10.2 g/dL, p = 0.01) and 24-hour postoperative Hb (7.7 g/dL, p < 0.001). Drain output between the transfusion and no transfusion groups varied significantly (p = 0.03), with transfusion patients having higher postoperative day 1 drain output of 362.6 mL and total drain output of 376.6 mL. In this series, postoperative drain use with concomitant weight-based IV TXA is shown to be safe and efficacious. We observed exceedingly low risk of postoperative transfusion compared with prior reports of drain use alone as well as preserved low rate of hemarthrosis that has previously been positively linked to drain use.

Direct links between resource availability and activity budget better reveal ecological patterns of endangered Coimbra-Filho's titi monkey.

Many primatological studies do not assess direct indexes of food availability to make inferences about behavioral strategies. We related the diet and behavior of a group of Callicebus coimbrai in northeastern Brazil to fruit availability indexes and compared this pattern between seasons (direct and indirect assessment of food availability) to assess whether direct and indirect approaches detect similar ecological patterns. We monitored the study group for 33 months (5 days/month) via scan sampling. The monthly availability of fruits and new leaves was recorded in phenological transects. Fruit availability varied across years based on fruit prevalence, and timing and duration of the abundant seasons. We did not find evidence of a time-minimizing strategy, since C. coimbrai did not change its activity levels according to food availability. However, the negative relationship between foraging and fruit availability indicates that C. coimbrai can compensate for the lower fruit availability by increasing the search for alternative food sources. Monthly fruit consumption was positively correlated to fruit availability and negatively related to the consumption of other food items. However, the behavioral and feeding profiles did not vary between seasons and were not related to rainfall levels. Primate studies should directly relate behavioral and feeding profiles to fruit availability indices, thus avoiding using seasons as proxies of food availability.

Transmission and Management of Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians in Select Ornamentals.

Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians are phytobacteria that induce crown gall and leafy gall disease, respectively, resulting in undesirable growth abnormalities. When present in nurseries, plants infected by either bacterium are destroyed, resulting in substantial losses for growers, especially those producing plants valued for their ornamental attributes. There are many unanswered questions regarding pathogen transmission on tools used to take cuttings for propagation and whether products used for bacterial disease control are effective. We investigated the ability to transmit pathogenic A. tumefaciens and R. fascians on secateurs and the efficacy of registered control products against both bacteria in vitro and in vivo. Experimental plants used were Rosa × hybrida, Leucanthemum × superbum, and Chrysanthemum × grandiflorum for A. tumefaciens and Petunia × hybrida and Oenothera 'Siskiyou' with R. fascians. In separate experiments, we found secateurs could convey both bacteria in numbers sufficient to initiate disease in a host-dependent manner and that bacteria could be recovered from secateurs after a single cut through an infected stem. In in vivo assays, none of six products tested against A. tumefaciens prevented crown gall disease, although several products appeared promising in in vitro trials. Likewise, four compounds trialed against R. fascians failed to prevent disease. Sanitation and clean planting material remain the primary means of disease management.

A clinical approach to the investigation and management of long COVID associated neuropathic pain.

COVID-19 has been associated with a wide range of ongoing symptoms following recovery from the acute SARS-CoV-2 infection. Around one in three people with COVID-19 develop neurological symptoms with many reporting neuropathic pain and associated symptoms, including paraesthesia, numbness, and dysesthesia. Whilst the pathophysiology of long COVID-19-associated neuropathic pain remains unclear, it is likely to be multifactorial. Early identification, exclusion of common alternative causes, and a biopsychosocial approach to the management of the symptoms can help in relieving the burden of disease and improving the quality of life for patients.

Arthroscopic knots: Suture and knot characterisation of modern polyblend suture materials.

Objective: The primary aim of this study was to explore the relationship between the biophysical structure and function of modern suture materials. Particularly the suture's ability to withstand the stressors of surgery and how the material properties affect knot stability. The secondary aim was to investigate the effect that different knots have on the suture material itself. This study builds on previous research assessing suture and knot characteristics but in modern Ultra High Molecular Weight Polyethylene (UHMWPE) materials currently in widespread clinical use in arthroscopic surgery. Methods: Three common UHMWPE sutures and one polyester suture were tested in both a dry and wet state using the Geelong, Nicky's, Surgeon's and Tautline knots. Tensile strength of knots was tested vertically at a 60 mm/min strain rate and 45 mm gauge length. Sutures were tied through a cannula around two 8 mm diameter circular bollards. Testing was conducted in a controlled environment temperature and humidity environment (20 ± 2 °C, 65 ± 2%). Results: No one knot type was optimal over all suture types. Mean tensile strength in both a dry and wet state and a low coefficient of variation (CV) in tensile strength in a wet state were considered as an indication of suitability. With Ethibond sutures this was the Geelong knot (CV:4.2%). With Orthocord sutures both the Geelong and Tautline knots (CV:4.2% and CV:11.9% respectively). With FiberWire sutures the Nickys and Tautline knots (CV:22.6% and CV:22.5% respectively). With ForceFiber sutures all four knots exhibited similar wet tensile strength with high variability showing that all should perform in a similar way invivo. Conclusions: This study demonstrates a statistically significant three-way interaction between polyblend suture materials, the knot and the environment. This has implications for knot security using the tested sutures in different environments, as one knot may not behave the same under all conditions.

Genetic and molecular analysis of stem rot (Sclerotinia sclerotiorum) resistance in Brassica napus (canola type).

Identifying the molecular and genetic basis of resistance to Sclerotinia stem rot (Sclerotinia sclerotiorum) is critical for developing long-term and cost-effective management of this disease in rapeseed/canola (Brassica napus). Current cultural or chemical management options provide, at best, only partial and/or sporadic control. Towards this, a B. napus breeding population (Mystic x Rainbow), including the parents, F1, F2, BC1P1 and BC1P2, was utilized in a field study to determine the inheritance pattern of Sclerotinia stem rot resistance (based on stem lesion length, SLL). Broad sense heritability was 0.58 for SLL and 0.44 for days to flowering (DTF). There was a significant negative correlation between SLL and stem diameter (SD) (r = -0.39) and between SLL and DTF (r = -0.28), suggesting co-selection of SD and DTF traits, along with SLL, should assist in improving overall resistance. Non-additive genetic variance was evident for SLL, DTF, and SD. In a genome wide association study (GWAS), a significant quantitative trait locus (QTL) was identified for SLL. Several putative candidate marker trait associations (MTA) were located within this QTL region. Overall, this study has provided valuable new understanding of inheritance of resistance to S. sclerotiorum, and has identified QTL, MTAs and transgressive segregants with high-level resistances. Together, these will foster more rapid selection for multiple traits associated with Sclerotinia stem rot resistance, by enabling breeders to make critical choices towards selecting/developing cultivars with enhanced resistance to this devastating pathogen.

First report of Spiroplasma citri associated with disease symptoms in field-grown hemp (Cannabis sativa L.) in the Pacific Northwest.

Hemp (Cannabis sativa L.) is grown for cannabinoid oil production in Oregon. During the 2021 and 2022 growing seasons, plants with leaf curling, puckering, chlorotic mosaic, fasciation, and vein clearing were observed in disease surveys of Oregon hemp fields (Fig. 1). Symptoms were present on 1-10% of 2-4-month-old plants in fields located in Benton, Clackamas, Deschutes, Jackson, Josephine, Lane, Linn, Marion, Morrow, and Polk counties between July and September. Leaf and stem samples were collected from 38 symptomatic plants. Symptoms resembled those caused by beet leafhopper-vectored (BLH, Circulifer tenellus Baker) curtovirus or phytoplasma infection. Therefore, total nucleic acids were extracted (Dellaporta et al. 1983) from leaf material, and PCR conducted on all 38 samples to detect curtovirus coat proteins (BCTV-1/2 primers; Rondon et al. 2016) and 16S rRNA of phytoplasmas (nested primers P1/P7 followed by FU/RU; Lorenz et al. 1995). No curtoviruses or phytoplasmas were detected in any samples. Spiroplasma citri is also transmitted by BLH, so PCR was conducted with primers targeting the putative P89 adhesin gene and spiralin gene of S. citri (Yokomi et al. 2008). For all samples, PCR using P89F/R primers resulted in a 707 bp amplicon, and a 675 bp amplicon with Spiralin-f/r primers. PCR products were purified with ExoSapIT (Applied Biosystems, Waltham, MA), and two representative samples (ScH1; ScH2) were Sanger sequenced (EuroFins, Lancaster, PA) in the forward and reverse direction. Pairwise aligned P89 sequences were found to be 99 to 100% (ScH1: 633/637 bp; ScH2: 654/654 bp) identical to S. citri accession KT377386. Aligned/span>spiralin sequences were found to be 99 to 100% (ScH1: 661/664 bp; ScH2: 647/647 bp) identical to S. citri accession CP013197 in the NCBI GenBank Database. All sequences were deposited into GenBank (accession no. OQ969983, OQ992766, OQ969984, OQ969986). Frozen leaf material from one sample was used to culture S. citri according to Lee and Davis (1984). Leaf tissue was surface sterilized for 60 s in 1% NaOCl in 70% ethanol, cut into pieces in LD8 broth, and incubated for 25 min at 25˚C. The solution was passed through a 0.45um filter and incubated for 14 days at 30°C with constant shaking (150 rpm). Then, cultures were centrifuged for 2 min at 12,000 rpm to pelletize, resuspended in 100µL sterile distilled water and passed through a 0.2um filter. From this culture, 2 µL of broth was used as template for both the P89F/R and Spiralin-f/r primer sets. Amplicons were purified and sequenced as above (accession nos. OQ969982, OQ969985). Leaf tissue from both representative samples (ScH1 and ScH2) were positive for S. citri using double antibody sandwich ELISA (Agdia, Inc., Elkhart, IN) following manufacturer instructions. These results from sequencing, culturing, and ELISA testing indicate the hemp samples were infected with S. citri. To our knowledge this is the first report of disease symptoms in hemp associated with S. citri in Oregon and the Pacific Northwest. Infection by S. citri can limit yield by reducing photosynthetic capability of the plant and distortion of plant growth. Other pathogens like curtoviruses and phytoplasmas have also been detected in hemp in Oregon and the U.S. (Hu 2021; Rivedal et al. 2022), and the addition of S. citri associated with disease symptoms indicates a need for BLH management research. This discovery has implications for arid regions with other S. citri hosts including cruciferous plants, carrots, and tree fruit crops, all of which were grown near the sampled hemp fields in this study.

Review of optical reporters of radiation effects in vivo: tools to quantify improvements in radiation delivery technique.

Significance: Radiation damage studies are used to optimize radiotherapy treatment techniques. Although biological indicators of damage are the best assays of effect, they are highly variable due to biological heterogeneity. The free radical radiochemistry can be assayed with optical reporters, allowing for high precision titration of techniques. Aim: We examine the optical reporters of radiochemistry to highlight those with the best potential for translational use in vivo, as surrogates for biological damage assays, to inform on mechanisms. Approach: A survey of the radical chemistry effects from reactive oxygen species (ROS) and oxygen itself was completed to link to DNA or biological damage. Optical reporters of ROS include fluorescent, phosphorescent, and bioluminescent molecules that have a variety of activation pathways, and each was reviewed for its in vivo translation potential. Results: There are molecular reporters of ROS having potential to report within living systems, including derivatives of luminol, 2'7'-dichlorofluorescein diacetate, Amplex Red, and fluorescein. None have unique specificity to singular ROS species. Macromolecular engineered reporters unique to specific ROS are emerging. The ability to directly measure oxygen via reporters, such as Oxyphor and protoporphyrin IX, is an opportunity to quantify the consumption of oxygen during ROS generation, and this translates from in vitro to in vivo use. Emerging techniques, such as ion particle beams, spatial fractionation, and ultra-high dose rate FLASH radiotherapy, provide the motivation for these studies. Conclusions: In vivo optical reporters of radiochemistry are quantitatively useful for comparing radiotherapy techniques, although their use comes at the cost of the unknown connection to the mechanisms of radiobiological damage. Still their lower measurement uncertainty, compared with biological response assay, makes them an invaluable tool. Linkage to DNA damage and biological damage is needed, and measures such as oxygen consumption serve as useful surrogate measures that translate to in vivo use.

Incidence of surgical rib fixation at chest wall injury society collaborative centers and a guide for expected number of cases (CWIS-CC1).

PURPOSE: Surgical stabilization of rib fractures (SSRF) improves outcomes in certain patient populations. The Chest Wall Injury Society (CWIS) began a new initiative to recognize centers who epitomize their mission as CWIS Collaborative Centers (CWIS-CC). We sought to describe incidence and epidemiology of SSRF at our institutions. METHODS: A retrospective registry evaluation of all patients (age > 15 years) treated at international trauma centers from 1/1/20 to 7/30/2021 was performed. Variables included: age, gender, mechanism of injury, injury severity score, abbreviated injury severity score (AIS), emergency department disposition, length of stay, presence of rib/sternal fractures, and surgical stabilization of rib/sternal fractures. Classification and regression tree analysis (CART) was used for analysis. RESULTS: Data were collected from 9 centers, 26,084 patient encounters. Rib fractures were present in 24% (n = 6294). Overall, 2% of all patients underwent SSRF and 8% of patients with rib fractures underwent SSRF. CART analysis of SSRF by AIS-Chest demonstrated a difference in management by age group. AIS-Chest 3 had an SSRF rate of 3.7, 7.3, and 12.9% based on the age ranges (16-19; 80-110), (20-49; 70-79), and (50-69), respectively (p = 0.003). AIS-Chest > 3 demonstrated an SSRF rate of 9.6, 23.3, and 39.3% for age ranges (16-39; 90-99), (40-49; 80-89), and (50-79), respectively (p = 0.001). CONCLUSION: Anticipated rate of SSRF can be calculated based on number of rib fractures, AIS-Chest, and age. The disproportionate rate of SSRF in patients age 50-69 with AIS-Chest 3 and age 50-79 with AIS-Chest > 3 should be further investigated, as lower frequency of SSRF in the other age ranges may lead to care inequalities.

A novel method of assessing balance and postural sway in patients with hypermobile Ehlers-Danlos syndrome.

Patients with hypermobile Ehlers-Danlos syndrome (hEDS) frequently suffer from poor balance and proprioception and are at an increased risk for falls. Here we present a means of assessing a variety of balance and postural conditions in a fast and non-invasive manner. The equipment required is commercially available and requires limited personnel. Patients can be repeatedly tested to determine balance and postural differences as a result of disease progression and aging, or a reversal following balance/exercise interventions.

Comparative pangenome analyses provide insights into the evolution of Brassica rapa resistance gene analogues (RGAs).

Brassica rapa is grown worldwide as economically important vegetable and oilseed crop. However, its production is challenged by yield-limiting pathogens. The sustainable control of these pathogens mainly relies on the deployment of genetic resistance primarily driven by resistance gene analogues (RGAs). While several studies have identified RGAs in B. rapa, these were mainly based on a single genome reference and do not represent the full range of RGA diversity in B. rapa. In this study, we utilized the B. rapa pangenome, constructed from 71 lines encompassing 12 morphotypes, to describe a comprehensive repertoire of RGAs in B. rapa. We show that 309 RGAs were affected by presence-absence variation (PAV) and 223 RGAs were missing from the reference genome. The transmembrane leucine-rich repeat (TM-LRR) RGA class had more core gene types than variable genes, while the opposite was observed for nucleotide-binding site leucine-rich repeats (NLRs). Comparative analysis with the B. napus pangenome revealed significant RGA conservation (93%) between the two species. We identified 138 candidate RGAs located within known B. rapa disease resistance QTL, of which the majority were under negative selection. Using blackleg gene homologues, we demonstrated how these genes in B. napus were derived from B. rapa. This further clarifies the genetic relationship of these loci, which may be useful in narrowing-down candidate blackleg resistance genes. This study provides a novel genomic resource towards the identification of candidate genes for breeding disease resistance in B. rapa and its relatives.

Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure.

The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or 'discs', located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep indentations in their rims called 'incisures'. The presence of incisures has been documented in a variety of species, yet their role remains elusive. In this study, we combined traditional electron microscopy with three-dimensional electron tomography to demonstrate that incisures are formed only after discs become completely enclosed. We also observed that, at the earliest stage of their formation, discs are not round as typically depicted but rather are highly irregular in shape and resemble expanding lamellipodia. Using genetically manipulated mice and frogs and measuring outer segment protein abundances by quantitative mass spectrometry, we further found that incisure size is determined by the molar ratio between peripherin-2, a disc rim protein critical for the process of disc enclosure, and rhodopsin, the major structural component of disc membranes. While a high perpherin-2 to rhodopsin ratio causes an increase in incisure size and structural complexity, a low ratio precludes incisure formation. Based on these data, we propose a model whereby normal rods express a modest excess of peripherin-2 over the amount required for complete disc enclosure in order to ensure that this important step of disc formation is accomplished. Once the disc is enclosed, the excess peripherin-2 incorporates into the rim to form an incisure.

Review article: Accuracy of emergency physician performed point-of-care ultrasound of the thoracic aorta: A systematic review and narrative synthesis of the literature.

Point-of-care ultrasound (POCUS) is becoming ubiquitous in emergency medicine. POCUS for abdominal aortic aneurysm is well established in practice. The thoracic aorta can also be assessed by POCUS for dissection and aneurysm and transthoracic echocardiography is endorsed by international guidelines as an initial test for thoracic aortic pathologies. A systematic search of Ovid Medline, PubMed, EMBASE, SCOPUS and Web of Science from January 2000 to August 2022 identified four studies evaluating diagnostic accuracy of emergency physician POCUS for thoracic aortic dissection (TAD) and five studies for thoracic aortic aneurysm (TAA). Study designs were heterogeneous including differing diagnostic criteria for aortic pathology. Convenience recruitment was frequent in prospective studies. Sensitivity and specificity ranges for studies of TAD were 41-91% and 94-100%, respectively when an intimal flap was seen. Sensitivity and specificity ranges for studies of thoracic aorta dilation >40 mm were 50-100% and 93-100%, respectively; for >45 mm ranges were 64-65% and 95-99%. Literature review identified that POCUS is specific for TAD and TAA. POCUS reduces the time to diagnosis of thoracic aortic pathology; however, it remains insensitive and cannot be recommended as a stand-alone rule-out test. We suggest that detection of thoracic aorta dilation >40 mm by POCUS at any site increases the suspicion of serious aortic pathology. Studies incorporating algorithmic use of POCUS, Aortic Dissection Detection Risk Score and D-dimer as decision tools are promising and may improve current ED practices. Further research is warranted in this rapidly evolving field.

CRISPR-Based Genome Editing Tools: An Accelerator in Crop Breeding for a Changing Future.

Genome editing is an important strategy to maintain global food security and achieve sustainable agricultural development. Among all genome editing tools, CRISPR-Cas is currently the most prevalent and offers the most promise. In this review, we summarize the development of CRISPR-Cas systems, outline their classification and distinctive features, delineate their natural mechanisms in plant genome editing and exemplify the applications in plant research. Both classical and recently discovered CRISPR-Cas systems are included, detailing the class, type, structures and functions of each. We conclude by highlighting the challenges that come with CRISPR-Cas and offer suggestions on how to tackle them. We believe the gene editing toolbox will be greatly enriched, providing new avenues for a more efficient and precise breeding of climate-resilient crops.

Role of the Coiled-Coil Domain in Allosteric Activity Regulation in Soluble Guanylate Cyclase.

Soluble guanylate cyclase (sGC) is the primary nitric oxide (NO) receptor in higher eukaryotes, including humans. NO-dependent signaling via sGC is associated with important physiological effects in the vascular, pulmonary, and neurological systems, and sGC itself is an established drug target for the treatment of pulmonary hypertension due to its central role in vasodilation. Despite isolation in the late 1970s, high-resolution structural information on full-length sGC remained elusive until recent cryo-electron microscopy structures were determined of the protein in both the basal unactivated state and the NO-activated state. These structures revealed large-scale conformational changes upon activation that appear to be centered on rearrangements within the coiled-coil (CC) domains in the enzyme. Here, a structure-guided approach was used to engineer constitutively unactivated and constitutively activated sGC variants through mutagenesis of the CC domains. These results demonstrate that the activation-induced conformational change in the CC domains is necessary and sufficient for determining the level of sGC activity.

Histological and MRI brain atlas of the common shrew, Sorex araneus, with brain region-specific gene expression profiles.

The common shrew, Sorex araneus, is a small mammal of growing interest in neuroscience research, as it exhibits dramatic and reversible seasonal changes in individual brain size and organization (a process known as Dehnel's phenomenon). Despite decades of studies on this system, the mechanisms behind the structural changes during Dehnel's phenomenon are not yet understood. To resolve these questions and foster research on this unique species, we present the first combined histological, magnetic resonance imaging (MRI), and transcriptomic atlas of the common shrew brain. Our integrated morphometric brain atlas provides easily obtainable and comparable anatomic structures, while transcriptomic mapping identified distinct expression profiles across most brain regions. These results suggest that high-resolution morphological and genetic research is pivotal for elucidating the mechanisms underlying Dehnel's phenomenon while providing a communal resource for continued research on a model of natural mammalian regeneration. Morphometric and NCBI Sequencing Read Archive are available at https://doi.org/10.17617/3.HVW8ZN.