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1.
Vet Surg ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38863141

ABSTRACT

OBJECTIVE: To describe the signalment, treatment, complications, and outcomes of cats treated surgically for ectopic ureters. STUDY DESIGN: Retrospective, multi-institutional study. ANIMALS: Twelve client-owned cats. METHODS: Medical records of cats diagnosed with unilateral or bilateral ectopic ureters were reviewed and analyzed. Data reported included signalment, clinical signs, diagnostics, open celiotomy, or cystoscopic surgical interventions, and outcomes. RESULTS: Seven of the 12 cats in the study population were female or female spayed and the median age at time of presentation was 4 years, with an interquartile range (IQR) of 6 months-14 years. Presurgical diagnostic imaging diagnosed ectopic ureters by abdominal ultrasound (8/10), contrast enhanced computed tomography (3/3), fluoroscopic urography (3/4), or cystoscopy (6/7). Eight of 12 cats had extramural ectopic ureters and six cats were affected bilaterally. Eight affected cats underwent ureteroneocystostomy, one cat underwent neoureterostomy, two cats underwent cystoscopic laser ablation, and one cat underwent nephroureterostomy. Immediate postoperative complications occurred in three cats; one cat required additional surgical intervention. Short-term complications occurred in three cats, and long-term complications in two cats. All cats that underwent surgical or cystoscopic intervention had improvement of their urinary incontinence scores, with complete resolution in 11 cats. CONCLUSION: Surgical correction of ectopic ureters in cats is associated with good long-term outcomes. Ectopic ureters in cats are commonly extramural and bilateral. Postoperative outcomes were acceptable and there were few postoperative complications, with varying forms of surgical correction. CLINICAL SIGNIFICANCE: Ectopic ureters in cats are rare but urinary incontinence can be corrected or improved successfully with surgery.

2.
Environ Manage ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834791

ABSTRACT

Recreational angling of nesting largemouth bass (Micropterus nigricans) and smallmouth bass (M. dolomieu) can greatly increase nest abandonment, and in the northern clines of their range, decrease recruitment. This is the case in eastern Ontario, where high levels of non-compliance and difficult to enforce regulations have impacted black bass (Micropterus spp.) conservation and management. Effective January 1, 2024 until December 31st, 2025, novel and experimental fishing sanctuaries were imposed on portions of Charleston Lake and Opinicon Lake that prohibit recreational fishing of all types from April 15th to the Friday before the first Saturday in July (encompassing the full bass reproductive season). As part of the formal process to institute these experimental regulations, public comments were collected on the Environmental Registry of Ontario. We examined those comments and identified supportive and non-supportive themes related to these experimental regulations. While a majority of stakeholders were in support of the new regulations, we also noted sub-themes that may hinder regulation acceptance. Those sub-themes include: a perceived lack of enforcement negating the potential benefits of the sanctuaries, under-estimation of the extent of non-compliance with existing regulations such that new regulations are unnecessary, misunderstanding and misinformation, as well as distrust of government and the academic research community. Understanding and addressing these stakeholder perspectives will help researchers studying the new sanctuary areas and managers understand any lack of compliance while informing future decisions about bass management in eastern Ontario and beyond.

3.
iScience ; 27(6): 109856, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38784019

ABSTRACT

Cells' structure is key to understanding cellular function, diagnostics, and therapy development. Soft X-ray tomography (SXT) is a unique tool to image cellular structure without fixation or labeling at high spatial resolution and throughput. Fast acquisition times increase demand for accelerated image analysis, like segmentation. Currently, segmenting cellular structures is done manually and is a major bottleneck in the SXT data analysis. This paper introduces ACSeg, an automated 3D cytoplasm segmentation model. ACSeg is generated using semi-automated labels and 3D U-Net and is trained on 43 SXT tomograms of immune T cells, rapidly converging to high-accuracy segmentation, therefore reducing time and labor. Furthermore, adding only 6 SXT tomograms of other cell types diversifies the model, showing potential for optimal experimental design. ACSeg successfully segmented unseen tomograms and is published on Biomedisa, enabling high-throughput analysis of cell volume and structure of cytoplasm in diverse cell types.

4.
Life Sci Alliance ; 7(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-38816213

ABSTRACT

In cells, mitochondria undergo constant fusion and fission. An essential factor for fission is the mammalian dynamin-related protein 1 (Drp1). Dysregulation of Drp1 is associated with neurodegenerative diseases including Parkinson's, cardiovascular diseases and cancer, making Drp1 a pivotal biomarker for monitoring mitochondrial status and potential pathophysiological conditions. Here, we developed nanobodies (Nbs) as versatile binding molecules for proteomics, advanced microscopy and live cell imaging of Drp1. To specifically enrich endogenous Drp1 with interacting proteins for proteomics, we functionalized high-affinity Nbs into advanced capture matrices. Furthermore, we detected Drp1 by bivalent Nbs combined with site-directed fluorophore labelling in super-resolution STORM microscopy. For real-time imaging of Drp1, we intracellularly expressed fluorescently labelled Nbs, so-called chromobodies (Cbs). To improve the signal-to-noise ratio, we further converted Cbs into a "turnover-accelerated" format. With these imaging probes, we visualized the dynamics of endogenous Drp1 upon compound-induced mitochondrial fission in living cells. Considering the wide range of research applications, the presented Nb toolset will open up new possibilities for advanced functional studies of Drp1 in disease-relevant models.


Subject(s)
Dynamins , Mitochondria , Mitochondrial Dynamics , Single-Domain Antibodies , Dynamins/metabolism , Humans , Single-Domain Antibodies/metabolism , Single-Domain Antibodies/immunology , Mitochondria/metabolism , Proteomics/methods , Animals , Protein Binding , HeLa Cells , Mitochondrial Proteins/metabolism
5.
J Am Vet Med Assoc ; 262(7): 1-9, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38382204

ABSTRACT

OBJECTIVE: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance. ANIMALS: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space. METHODS: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed to report descriptive data for all cases and overall survival time. Multivariate analysis was utilized to evaluate prognostic factors for overall survival. RESULTS: Hemangiosarcoma was the most common histologic subtype diagnosed (76.1%). Cytoreductive and curative intent surgical excision of the RPS was attempted in 12 and 22 dogs, respectively; 12 dogs underwent no surgery or had an exploratory laparotomy with incisional biopsy only. Nineteen dogs received adjuvant chemotherapy, either injectable or metronomic, and 1 dog received adjuvant radiation therapy. Fourteen of the 34 (41.2%) surgically treated dogs developed evidence of local recurrence, but there was no difference in local recurrence when comparing dogs categorized as curative intent versus cytoreductive surgery. The median overall survival time was 238 days. On multivariable analysis, treatment approach was associated with survival with surgical excision (vs palliative treatment) and adjuvant chemotherapy following surgery being protective against death. A diagnosis of hemangiosarcoma was associated with a greater hazard of death. CLINICAL RELEVANCE: This study demonstrates a substantially greater survival time than previously published and suggests a survival benefit from surgical excision and adjuvant chemotherapy.


Subject(s)
Dog Diseases , Retroperitoneal Neoplasms , Sarcoma , Animals , Dogs , Dog Diseases/therapy , Dog Diseases/mortality , Dog Diseases/surgery , Dog Diseases/pathology , Sarcoma/veterinary , Sarcoma/therapy , Sarcoma/mortality , Sarcoma/surgery , Retroperitoneal Neoplasms/veterinary , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/surgery , Retroperitoneal Neoplasms/therapy , Retroperitoneal Neoplasms/pathology , Male , Female , Retrospective Studies , Treatment Outcome , Survival Analysis , Cohort Studies , Hemangiosarcoma/veterinary , Hemangiosarcoma/mortality , Hemangiosarcoma/therapy , Hemangiosarcoma/surgery , Hemangiosarcoma/pathology
6.
J Am Vet Med Assoc ; 262(5): 674-679, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38335731

ABSTRACT

OBJECTIVE: To report and evaluate risk factors for conversion and perioperative and long-term outcomes in dogs undergoing thoracoscopic lung lobectomy for resection of lung masses. ANIMALS: 61 client-owned dogs. METHODS: This retrospective cohort study (June 11, 2008, to February 14, 2020) of data collected from medical records included signalment, results of diagnostic imaging, surgical technique, surgical and anesthesia time, mass location and size, hospitalization time, histopathologic findings, and long-term outcome. Follow-up was obtained from medical records and telephone contact with owners or referring veterinarians. RESULTS: Histopathology results were available for 60 of 61 tumors. Fifty-seven (95%) were considered primary lung tumors, of which 46 (81%) were carcinomas. Clean surgical margins were achieved in 46 of 52 (88%) dogs. Conversion from thoracoscopy to thoracoscopic-assisted or open surgery occurred in 16 of 61 (26%) dogs. Larger tumor diameter (≥ 5 cm) and lymphadenopathy detected by preoperative CT scan were significantly associated with increased risk of conversion. There was no association between conversion and patient weight, body condition score, and tumor location. All 61 dogs survived to discharge, and 56 of 57 were alive 1 month postoperatively. Median overall survival time was 311 days (95% CI, 224 to 570 days). Tracheobronchial lymphadenopathy on preoperative CT scans was associated with shorter postoperative survival (P < .001). Patient age, tumor diameter, adjuvant chemotherapy following surgery, and incomplete margins were not associated with survival time. CLINICAL RELEVANCE: Dogs had high survival to discharge and good long-term prognosis following thoracoscopic lung lobectomy. However, larger tumor size and tracheobronchial lymphadenopathy may increase the likelihood of conversion.

7.
J Hazard Mater ; 465: 133218, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38113738

ABSTRACT

Laboratory studies show detrimental effects of metallic pollutants on invertebrate behaviour and cognition, even at low levels. Here we report a field study on Western honey bees exposed to metal and metalloid pollution through dusts, food and water at a historic mining site. We analysed more than 1000 bees from five apiaries along a gradient of contamination within 11 km of a former gold mine in Southern France. Bees collected close to the mine exhibited olfactory learning performances lower by 36% and heads smaller by 4%. Three-dimensional scans of bee brains showed that the olfactory centres of insects sampled close to the mine were also 4% smaller, indicating neurodevelopmental issues. Our study raises serious concerns about the health of honey bee populations in areas polluted with potentially harmful elements, particularly with arsenic, and illustrates how standard cognitive tests can be used for risk assessment.


Subject(s)
Environmental Pollutants , Environmental Pollution , Bees , Animals , Environmental Exposure , Cognition , Environmental Pollutants/analysis , Brain
8.
Anesthesiology ; 140(5): 1002-1015, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38157435

ABSTRACT

BACKGROUND: Thermodilution is unreliable in veno-venous extracorporeal membrane oxygenation (VV-ECMO). Systemic oxygenation depends on recirculation fractions and ratios of extracorporeal membrane oxygenation (ECMO) flow to cardiac output. In a prospective in vitro simulation, this study assessed the diagnostic accuracy of a modified thermodilution technique for recirculation and cardiac output. The hypothesis was that this method provided clinically acceptable precision and accuracy for cardiac output and recirculation. METHODS: Two ECMO circuits ran in parallel: one representing a VV-ECMO and the second representing native heart, lung, and circulation. Both circuits shared the right atrium. Extra limbs for recirculation and pulmonary shunt were added. This study simulated ECMO flows from 1 to 2.5 l/min and cardiac outputs from 2.5 to 3.5 l/min with recirculation fractions (0 to 80%) and pulmonary shunts. Thermistors in both ECMO limbs and the pulmonary artery measured the temperature changes induced by cold bolus injections into the arterial ECMO limb. Recirculation fractions were calculated from the ratio of the areas under the temperature curve (AUCs) in the ECMO limbs and from partitioning of the bolus volume (flow based). With known partitioning of bolus volumes between ECMO and pulmonary artery, cardiac output was calculated. High-precision ultrasonic flow probes served as reference for Bland-Altman plots and linear mixed-effect models. RESULTS: Accuracy and precision for both the recirculation fraction based on AUC (bias, -5.4%; limits of agreement, -18.6 to 7.9%) and flow based (bias, -5.9%; limits of agreement, -18.8 to 7.0%) are clinically acceptable. Calculated cardiac output for all recirculation fractions was accurate but imprecise (RecirculationAUC: bias 0.56 l/min; limits of agreement, -2.27 to 3.4 l/min; and RecirculationFLOW: bias 0.48 l/min; limits of agreement, -2.22 to 3.19 l/min). Recirculation fraction increased bias and decreased precision. CONCLUSIONS: Adapted thermodilution for VV-ECMO allows simultaneous measurement of recirculation fraction and cardiac output and may help optimize patient management with severe respiratory failure.


Subject(s)
Extracorporeal Membrane Oxygenation , Humans , Extracorporeal Membrane Oxygenation/methods , Thermodilution/methods , Prospective Studies , Cardiac Output , Lung
9.
PLoS One ; 18(11): e0294896, 2023.
Article in English | MEDLINE | ID: mdl-38019829

ABSTRACT

The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of respondents living in private households in Germany. The dataset offers a valuable life course panorama, encompassing living conditions, socioeconomic status, familial connections, personality traits, values, preferences, health, and well-being. To amplify research opportunities further, we have extended the SOEP Innovation Sample (SOEP-IS) by collecting genetic data from 2,598 participants, yielding the first genotyped dataset for Germany based on a representative population sample (SOEP-G). The sample includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 triads, which overlap with the parent-offspring pairs. Leveraging the results from well-powered genome-wide association studies, we created a repository comprising 66 polygenic indices (PGIs) in the SOEP-G sample. We show that the PGIs for height, BMI, and educational attainment capture 22∼24%, 12∼13%, and 9% of the variance in the respective phenotypes. Using the PGIs for height and BMI, we demonstrate that the considerable increase in average height and the decrease in average BMI in more recent birth cohorts cannot be attributed to genetic shifts within the German population or to age effects alone. These findings suggest an important role of improved environmental conditions in driving these changes. Furthermore, we show that higher values in the PGIs for educational attainment and the highest math class are associated with better self-rated health, illustrating complex relationships between genetics, cognition, behavior, socio-economic status, and health. In summary, the SOEP-G data and the PGI repository we created provide a valuable resource for studying individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and the environment.


Subject(s)
Academic Success , Genome-Wide Association Study , Humans , Educational Status , Individuality , Germany/epidemiology , Socioeconomic Factors
10.
PLoS Comput Biol ; 19(10): e1011529, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37782674

ABSTRACT

Analysing large numbers of brain samples can reveal minor, but statistically and biologically relevant variations in brain morphology that provide critical insights into animal behaviour, ecology and evolution. So far, however, such analyses have required extensive manual effort, which considerably limits the scope for comparative research. Here we used micro-CT imaging and deep learning to perform automated analyses of 3D image data from 187 honey bee and bumblebee brains. We revealed strong inter-individual variations in total brain size that are consistent across colonies and species, and may underpin behavioural variability central to complex social organisations. In addition, the bumblebee dataset showed a significant level of lateralization in optic and antennal lobes, providing a potential explanation for reported variations in visual and olfactory learning. Our fast, robust and user-friendly approach holds considerable promises for carrying out large-scale quantitative neuroanatomical comparisons across a wider range of animals. Ultimately, this will help address fundamental unresolved questions related to the evolution of animal brains and cognition.


Subject(s)
Deep Learning , Bees , Animals , X-Ray Microtomography , Organ Size , Brain/diagnostic imaging , Brain/anatomy & histology , Cognition
11.
Behav Genet ; 53(5-6): 404-415, 2023 11.
Article in English | MEDLINE | ID: mdl-37713023

ABSTRACT

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, although down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci; the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses were found robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who generate and share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers' use of the summary statistics.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide/genetics , Phenotype , Genomics/methods , Multifactorial Inheritance
12.
J Am Soc Mass Spectrom ; 34(11): 2556-2566, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37756257

ABSTRACT

Protein glycosylation is one of the most common PTMs and many cell surface receptors, extracellular proteins, and biopharmaceuticals are glycosylated. However, HDX-MS analysis of such important glycoproteins has so far been limited by difficulties in determining the HDX of the protein segments that contain glycans. We have developed a column containing immobilized PNGase Rc (from Rudaea cellulosilytica) that can readily be implemented into a conventional HDX-MS setup to allow improved analysis of glycoproteins. We show that HDX-MS with the PNGase Rc column enables efficient online removal of N-linked glycans and the determination of the HDX of glycosylated regions in several complex glycoproteins. Additionally, we use the PNGase Rc column to perform a comprehensive HDX-MS mapping of the binding epitope of a mAb to c-Met, a complex glycoprotein drug target. Importantly, the column retains high activity in the presence of common quench-buffer additives like TCEP and urea and performed consistent across 114 days of extensive use. Overall, our work shows that HDX-MS with the integrated PNGase Rc column can enable fast and efficient online deglycosylation at harsh quench conditions to provide comprehensive analysis of complex glycoproteins.


Subject(s)
Glycoproteins , Polysaccharides , Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase , Glycoproteins/analysis , Glycosylation , Polysaccharides/metabolism
13.
World J Urol ; 41(8): 2091-2097, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37528288

ABSTRACT

PURPOSE: Determining the frequency and distribution of pathogenic germline variants (PGVs) in Austrian prostate cancer (PCa) patients and to assess the accuracy of different clinical risk scores to correctly predict PGVs. METHODS: This cross-sectional study included 313 men with advanced PCa. A comprehensive personal and family history was obtained based on predefined questionnaires. Germline DNA sequencing was performed between 2019 and 2021 irrespective of family history, metastatic or castration status or age at diagnosis. Clinical risk scores for hereditary cancer syndromes were evaluated and a PCa-specific score was developed to assess the presence of PGVs. RESULTS: PGV presence was associated with metastasis (p = 0.047) and castration resistance (p = 0.011), but not with personal cancer history or with relatives with any type of cancer. Clinical risk scores (Manchester score, PREMM5 score, Amsterdam II criteria or Johns Hopkins criteria) showed low sensitivities (3.3-20%) for assessing the probability of PGV presence. A score specifically designed for PCa patients stratifying patients into low- or high-risk regarding PGV probability, correctly classified all PGV carriers as high-risk, whereas a third of PCa patients without PGVs was classified as low risk of the presence of PGVs. CONCLUSION: Application of common clinical risk scores based on family history are not suitable to identify PCa patients with high PGV probabilities. A PCa-specific score stratified PCa patients into low- or high-risk of PGV presence with sufficient accuracy, and germline DNA sequencing may be omitted in patients with a low score. Further studies are needed to evaluate the score.


Subject(s)
Prostatic Neoplasms , Male , Humans , Cross-Sectional Studies , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Risk Factors , Germ Cells/pathology , Austria , Genetic Predisposition to Disease
14.
Microsc Microanal ; 29(29 Suppl 1): 1173-1174, 2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37613163
15.
Microsc Microanal ; 29(29 Suppl 1): 1168-1169, 2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37613336
16.
J Am Vet Med Assoc ; 261(12): 1-8, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37582487

ABSTRACT

OBJECTIVE: To report the short- and long-term outcomes of laparoscopic adrenalectomy (LA) for resection of unilateral adrenal masses and to document risk factors for conversion and peri- and postoperative morbidity. ANIMALS: 255 client-owned dogs. METHODS: Dogs were included if LA was attempted for resection of a unilateral adrenal mass. Medical records were evaluated and relevant data were reported, including complications, conversion, perioperative death, and long-term outcomes. Signalment, clinicopathological data, and surgical experience were factors statistically evaluated for possible associations with capsular penetration during surgery, conversion, surgical time, duration of hospital stay, death prior to discharge, mass recurrence, and survival time. RESULTS: 155 dogs had left-sided tumors, and 100 had right-sided tumors. Conversion to an open approach was performed in 9.4% of cases. Capsular penetration (19.2%) and major hemorrhage (5.4%) were the most prevalent intraoperative complications. Of the dogs operated on, 94.9% were discharged from the hospital. Lesion side, portion of the gland affected, and surgeon experience influenced surgical time. Conversion rate increased with increasing body condition score and lesion size. Risk of death prior to discharge increased with increasing lesion size. Risk of conversion and death prior to discharge were lower when performed by more experienced surgeons. Capsular penetration during LA increased the risk of tumor recurrence. CLINICAL RELEVANCE: LA for resection of unilateral adrenal masses is associated with excellent outcomes in experienced centers. Surgeons with greater experience with LA have lower surgical times, conversion rates, and risk of death prior to discharge.


Subject(s)
Adrenal Gland Neoplasms , Dog Diseases , Laparoscopy , Humans , Dogs , Animals , Adrenalectomy/veterinary , Laparoscopy/veterinary , Retrospective Studies , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/veterinary , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/veterinary , Adrenal Gland Neoplasms/pathology , Dog Diseases/surgery
17.
Biochim Biophys Acta Bioenerg ; 1864(4): 148996, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37437858

ABSTRACT

Using ultrafast spectroscopy and site-specific mutagenesis, we demonstrate the central role of a conserved tyrosine within the chromophore binding pocket in the forward (Pr â†’ Pfr) photoconversion of phytochromes. Taking GAF1 of the knotless phytochrome All2699g1 from Nostoc as representative member of phytochromes, it was found that the mutations have no influence on the early (<30 ps) dynamics associated with conformational changes of the chromophore in the excited state. Conversely, they drastically impact the extended protein-controlled excited state decay (>100 ps). Thus, the steric demand, position and H-bonding capabilities of the identified tyrosine control the chromophore photoisomerization while leaving the excited state chromophore dynamics unaffected. In effect, this residue operates as an isomerization-steric-gate that tunes the excited state lifetime and the photoreaction efficiency by modulating the available space of the chromophore and by stabilizing the primary intermediate Lumi-R. Understanding the role of such a conserved structural element sheds light on a key aspect of phytochrome functionality and provides a basis for rational design of optimized photoreceptors for biotechnological applications.


Subject(s)
Biochemical Phenomena , Phytochrome , Phytochrome/genetics , Phytochrome/metabolism , Tyrosine , Hydrogen Bonding , Spectrum Analysis
18.
J Am Vet Med Assoc ; 261(10): 1-5, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37290759

ABSTRACT

OBJECTIVE: To report perioperative characteristics and outcome following bilateral, single-session, laparoscopic adrenalectomy (BSSLA) in dogs. ANIMALS: Client-owned dogs (n = 6). CLINICAL PRESENTATION AND PROCEDURES: Medical records were reviewed and perioperative data collected, including preoperative diagnostic imaging, operative details, complications, and need for conversion to open laparotomy. Bilateral, single-session, laparoscopic adrenalectomy was performed on the right or left side with a standard 3- or 4-portal transperitoneal technique. The dog was repositioned to contralateral recumbency, and laparoscopic adrenalectomy was repeated. Follow-up information was collected by telephone interviews with the owners and/or referring veterinarian. RESULTS: Median age and weight of dogs were 126 months and 14.75 kg, respectively. Contrast-enhanced CT (CECT) was performed in all dogs. Median maximal tumor diameter was 2.6 and 2.3 cm for the right and left-sided tumors, respectively. Median surgical and anesthesia times were 158 and 240 minutes, respectively. Conversion to open laparotomy was performed in 1 dog following renal vein laceration during initial adrenalectomy. Left adrenalectomy and ureteronephrectomy were performed, and the right adrenal tumor was left in situ. Cardiac arrest occurred in 1 dog following initial adrenalectomy (left); however, the dog was resuscitated successfully, and contralateral laparoscopic adrenalectomy was performed without complication. All dogs survived to hospital discharge. Follow-up ranged from 60 to 730 days (median, 264 days) for dogs that successfully underwent BSSLA. CLINICAL RELEVANCE: BSSLA was associated with favorable outcomes in this cohort of dogs. Laparoscopy may be considered in dogs with bilateral, modestly sized, noninvasive adrenal tumors.


Subject(s)
Adrenal Gland Neoplasms , Dog Diseases , Laparoscopy , Dogs , Animals , Adrenalectomy/veterinary , Adrenalectomy/methods , Retrospective Studies , Laparoscopy/veterinary , Laparoscopy/methods , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/veterinary , Laparotomy/veterinary , Dog Diseases/surgery
19.
J Am Vet Med Assoc ; 261(10): 1-8, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37225157

ABSTRACT

OBJECTIVE: To evaluate short- and long-term outcomes for dogs undergoing anal sacculectomy for massive (> 5 cm) apocrine gland anal sac adenocarcinoma (AGASACA). ANIMALS: 28 client-owned dogs with massive AGASACA. PROCEDURES: A retrospective multi-institutional study was performed. Pre-, intra-, and post-operative data was collected, and variables were statistically analyzed for associations with progression-free interval (PFI) and overall survival (OS). RESULTS: At the time of anal sacculectomy, 19 (68%) dogs underwent concurrent iliosacral lymph node extirpation, including 17 of 18 (94%) dogs with suspected nodal metastasis preoperatively. Five (18%) dogs experienced grade 2 intraoperative complications. Ten (36%) dogs experienced postoperative complications, including 1 grade 3 and 1 grade 4 complication. No dogs had permanent fecal incontinence, tenesmus, or anal stenosis. Nineteen dogs received adjuvant chemotherapy, radiation, or both. Local recurrence occurred in 37% of dogs. Dogs with lymph node metastasis at surgery were more likely than dogs without metastasis to develop new/progressive lymph node metastasis (10/17 [59%] vs 0/10 [0%]; P = .003) and distant metastasis (7/17 [41%] vs 0/10 [0%]; P = .026). Median PFI was 204 days (95% CI, 145 to 392). Median OS was 671 days (95% CI, 225 to upper limit not reached). Nodal metastasis at the time of surgery was associated with shorter PFI (P = .017) but not OS (P = .26). Adjuvant therapy was not associated with outcome. CLINICAL RELEVANCE: Dogs with massive AGASACA experienced prolonged survival following anal sacculectomy despite a high incidence of local recurrence and metastasis. Lymph node metastasis at the time of surgery was a negative prognostic indicator for PFI but not OS.


Subject(s)
Adenocarcinoma , Anal Gland Neoplasms , Anal Sacs , Dog Diseases , Animals , Dogs , Adenocarcinoma/surgery , Adenocarcinoma/veterinary , Adenocarcinoma/drug therapy , Anal Gland Neoplasms/surgery , Anal Gland Neoplasms/pathology , Anal Sacs/surgery , Anal Sacs/pathology , Apocrine Glands/pathology , Dog Diseases/pathology , Lymphatic Metastasis/pathology , Retrospective Studies
20.
bioRxiv ; 2023 Mar 24.
Article in English | MEDLINE | ID: mdl-36993611

ABSTRACT

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci, while the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses are robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers' use of the summary statistics.

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