Parallel Loss Research Articles

Optimizing flotation froth image segmentation via parallel branch network and hybrid loss supervision

Flotation is a crucial technology for fine coal separation, and accurately acquiring bubble size information during the flotation process is essential for monitoring flotation conditions and achieving intelligent control. However, existing semantic segmentation models encountered issues with boundary disconnection when segmenting flotation bubbles, resulting in deviations between the extracted bubble sizes and their true values. To address the aforementioned challenges, a semantic segmentation model was proposed to maintain high-resolution feature maps throughout the network by designing a parallel branch network structure. Additionally, a ConvTranspose module was proposed to preserve the detailed feature information of images while gradually enhancing the resolution of feature maps. In the model training phase, a hybrid loss function combining pixel classification loss with shape similarity loss was proposed to alleviate the sample imbalance problem caused by the substantial difference in the number of pixels between bubble boundaries and the interior of bubbles. Moreover, since traditional semantic segmentation evaluation metrics, such as MIoU, lack a mechanism for measuring bubble boundary continuity and cannot effectively penalize the problem of boundary disconnection, this paper proposed a new evaluation method for assessing the segmentation performance of flotation froth images. To comprehensively evaluate the effectiveness of the proposed method, this paper conducted tests using flotation froth images collected from actual production processes. Compared with existing methods, the segmentation model proposed in this paper exhibited clear superiority in mitigating the problem of bubble boundary disconnection. The prediction error for the number of bubbles was 6.38 %, which is significantly better than other methods.

MASSIVE HEMORRHAGE DUE TO RUPTURE OF A RIGHT ILIAC ANEURYSM REVEALING BEHCET'S DISEASE: A CASE REPORT FROM THE FESTOC CENTER IN BAMAKO

INTRODUCTION: Behçet's disease is a chronic inflammatory disorder. It is clinically characterized by oral and genital aphthoses; skin lesions and systemic manifestations. Arterial aneurysms are defined as a loss of parallelism of the arterial walls, localized to an arterial segment, and corresponding to an increase of at least 50% of the normal arterial diameter. We report a case of Behcet's disease revealed by a ruptured aneurysm of the right primitive iliac artery. OBSERVATION: This was a 44-year-old patient with no known history, referred for management of a right inguinal mass that had progressively increased in volume and had been evolving for about 1 month. On admission, the physical examination revealed conjunctival pallor, a pulsatile right inguinal mass approximately 10 cm in diameter, and a suppurating sore on the scrotum. Doppler ultrasound of the lower limbs revealed an aneurysm of the right common iliac artery. The aneurysm ruptured during the short preparation period for surgery, resulting in cataclysmic hemorrhage. This prompted manual compression and the transfusion of several packed red blood cells. During transport to the OR, the patient experienced hemorrhagic shock and altered consciousness, prompting the administration of drugs (noradrenaline) and emergency orotracheal intubation. The aneurysm was controlled upstream and downstream by approaching the right primitive iliac artery, followed by dissection and clamping after general heparinization. The common femoral artery was then approached and checked. Surgical exploration revealed numerous clots which were evacuated, revealing a large neck extending over 7 cm. The procedure involved reconstruction of the common femoral artery with a patch saphenous graft and excision of the necrotic tissue. The post-operative course was marked by suppuration of the surgical wound, which progressed well with appropriate antibiotics and local care. CONCLUSION: Arterial involvement in Behçet's disease manifests as arterial thrombosis or, more frequently, aneurysm. This is due to inflammation of the media, intima and vasa vasorum. Their management can be envisaged in our context.

Enhancing Jujube Forest Growth Estimation and Disease Detection Using a Novel Diffusion-Transformer Architecture.

This paper proposes an advanced deep learning model that integrates the Diffusion-Transformer structure and parallel attention mechanism for the tasks of growth estimation and disease detection in jujube forests. Existing methods in forestry monitoring often fall short in meeting the practical needs of large-scale and highly complex forest areas due to limitations in data processing capabilities and feature extraction precision. In response to this challenge, this paper designs and conducts a series of benchmark tests and ablation experiments to systematically evaluate and verify the performance of the proposed model across key performance metrics such as precision, recall, accuracy, and F1-score. Experimental results demonstrate that compared to traditional machine learning models like Support Vector Machines and Random Forests, as well as common deep learning models such as AlexNet and ResNet, the model proposed in this paper achieves a precision of 95%, a recall of 92%, an accuracy of 93%, and an F1-score of 94% in the task of disease detection in jujube forests, showing similarly superior performance in growth estimation tasks as well. Furthermore, ablation experiments with different attention mechanisms and loss functions further validate the effectiveness of parallel attention and parallel loss function in enhancing the overall performance of the model. These research findings not only provide a new technical path for forestry disease monitoring and health assessment but also contribute rich theoretical and experimental foundations for related fields.

Parallel loss of sexual reproduction in field populations of a brown alga sheds light on the mechanisms underlying the emergence of asexuality.

Sexual reproduction is widespread, but asexual lineages have repeatedly arisen from sexual ancestors across a wide range of eukaryotic taxa. The molecular changes underpinning the switch to asexuality remain elusive, particularly in organisms with haploid sexual systems. Here we explore independent events of loss of sex in the brown alga Scytosiphon, examine the proximate and evolutionary mechanisms involved, and test the importance of sexual conflict on gene expression changes following loss of sex. We find that asexual females ('Amazons') lose ability to produce sex pheromone and, consequently, are incapable of attracting males, whereas they gain rapid parthenogenic development from large, unfertilized eggs. These phenotypic changes are accompanied by convergent changes in gene expression. Decay of female functions, rather than relaxation of sexual antagonism, may be a dominant force at play during the emergence of asexuality in haploid sexual systems. Moreover, we show that haploid purifying selection plays a key role in limiting the accumulation of deleterious alleles in Amazons, and we identify an autosomal locus associated with the Amazon phenotype. The sex chromosome, together with this autosomal locus, may underlie the switch to obligate asexuality in the Amazon populations.

The overlooked biodiversity loss

As most life-forms exist as holobionts, reduction of host-level biodiversity drives parallel habitat losses to their host-adapted microorganisms. The holobiont concept helps us to understand how species are habitats for – often ignored – coevolved microorganisms also worthy of conservation. Indeed, loss of host-associated microbial biodiversity may accelerate the extinction risks of their host.

Phylogenomics of the pantropical Connaraceae: revised infrafamilial classification and the evolution of heterostyly

Connaraceae is a pantropical family of about 200 species containing lianas and small trees with remarkably diverse floral polymorphisms, including distyly, tristyly, homostyly, and dioecy. To date, relationships within the family have not been investigated using a targeted molecular phylogenetic treatment, severely limiting systematic understanding and reconstruction of trait evolution. Accordingly, their last infrafamilial classification was based only on morphological data. Here, we used phylogenomic data obtained using the Angiosperms353 nuclear target sequence capture probes, sampling all tribes and almost all genera, entirely from herbarium specimens, to revise infrafamilial classification and investigate the evolution of heterostyly. The backbone of the resulting molecular phylogenetic tree is almost entirely resolved. Connaraceae consists of two clades, one containing only the African genus Manotes (4 or 5 species), which we newly recognize at the subfamily level. Vegetative and reproductive synapomorphies are proposed for Manotoideae. Within Connaroideae, Connareae is expanded to include the former Jollydoreae. The backbone of Cnestideae, which contains more than half of the Connaraceae species, remains incompletely resolved. Reconstructions of reproductive system evolution are presented that tentatively support tristyly as the ancestral state for the family, with multiple parallel losses, in agreement with previous hypotheses, plus possible re-gains. However, the great diversity of stylar polymorphisms and their phylogenetic lability preclude a definitive answer. Overall, this study reinforces the usefulness of herbarium phylogenomics, and unlocks the reproductive diversity of Connaraceae as a model system for the evolution of complex biological phenomena.

Evolutionary paths toward multi-level convergence of lactic acid bacteria in fructose-rich environments

Convergence provides clues to unveil the non-random nature of evolution. Intermediate paths toward convergence inform us of the stochasticity and the constraint of evolutionary processes. Although previous studies have suggested that substantial constraints exist in microevolutionary paths, it remains unclear whether macroevolutionary convergence follows stochastic or constrained paths. Here, we performed comparative genomics for hundreds of lactic acid bacteria (LAB) species, including clades showing a convergent gene repertoire and sharing fructose-rich habitats. By adopting phylogenetic comparative methods we showed that the genomic convergence of distinct fructophilic LAB (FLAB) lineages was caused by parallel losses of more than a hundred orthologs and the gene losses followed significantly similar orders. Our results further suggested that the loss of adhE, a key gene for phenotypic convergence to FLAB, follows a specific evolutionary path of domain architecture decay and amino acid substitutions in multiple LAB lineages sharing fructose-rich habitats. These findings unveiled the constrained evolutionary paths toward the convergence of free-living bacterial clades at the genomic and molecular levels.

Enfoque metodológico para el aprovechamiento de mermas de transformación agrícola basado en manufactura esbelta: Caso de estudio en una finca cafetera en Colombia

Improvements in production systems that use the lean manufacturing approach known as “Lean” have the objective of eliminating or reducing waste or process inefficiencies (muda). This approach is increasingly adopted by different industrial sectors, including agriculture. Although Lean improvements are traditionally applied to existing processes from cultivation to distribution, opportunities to intervene in processing wastes (losses) are left aside. This article presents a methodological approach framed in five Lean principles, made up of six activities aimed at the design of new processes that make use of the losses generated by harvesting and agricultural transformation. The methodological approach is applied in a Colombian coffee farm where parchment coffee transformation processes are developed. A parallel losses composting process is designed that transforms defective, green, overripe beans, coffee pulp, mucilage and husk. The results show that by applying the methodological approach on the coffee farm, a level of losses transformation of 86% is achieved. Molting is also reduced for both the current parchment coffee production line and the composting line to 35% and 50% respectively. The main reductions are reprocessing and waiting times. Finally, a 30.3% reduction is obtained in the time of activities that do not add value, making both the current and proposed processes more efficient and with better delivery times.

Litchi postharvest physiology and handling

AbstractLitchi (Litchi chinensis Sonn.) fruit, with its bright red color and sweet and juicy aril, is an important fruit crop in Asia, Africa, Australia, and South America. A major cause of the postharvest loss of litchi fruit is browning and decay. Chlorophyll breakdown and flavonoid synthesis occur simultaneously during the maturation of this nonclimacteric fruit. However, once litchi fruit is harvested, pericarp desiccation and membrane breakdown occur, which leads to browning with the rate of browning and later microcracking paralleling water loss rate. In addition, chilling injury can contribute to and increase pericarp browning and membrane leakage. Polyphenol oxidase and peroxidase are possibly key enzymes in the early stages of browning. An increase in the leakage of the pericarp membrane also occurs that correlates with browning. Many chemical treatments have been evaluated to retard pericarp browning, such as melatonin, hot water, acidified calcium sulfate (ACS), adenosine triphosphate, and tea seed oil. During long distance transportation, chemical treatments that involve sulfur are used, including SO2 fumigation, acid dip after SO2 fumigation, SO2 fumigation and sulfur sheet package, or SO2 fumigation followed by controlled atmosphere (CA), if approved by the importing country. Other treatments that avoid the use of SO2 include melatonin, ACS, and hot water brushing combined with an acid dip, CA, and modified atmosphere packaging. Anthracnose is a common disease that accelerates browning and decay. Penicillium species as a saprophyte is also common with fruit infection occurring in the field, during harvest, in the packhouse, cold rooms, and shipping containers. Sulfur sheet or CA is used to reduce fruit rot after SO2 fumigation and Sportak (prochloraz) for the control of penicillium. However, a replacement for postharvest SO2 use is still urgently needed.

MCTrans++: a 0-D model for centrifugal mirrors

The centrifugal mirror confinement scheme incorporates supersonic rotation of a plasma into a magnetic mirror device. This concept has been shown experimentally to drastically decrease parallel losses and increase plasma stability as compared with prior axisymmetric mirrors. MCTrans++ is a dimensionless (0-D) scoping tool which rapidly models experimental operating points in the Centrifugal Mirror Fusion Experiment (CMFX) at the University of Maryland. In the low-collisionality regime, parallel losses can be modelled analytically. A confining potential is set up that is partially ambipolar and partially centrifugal. Due to the stabilizing effects of flow shear, the perpendicular losses can be modelled as classical. Radiation losses such as bremsstrahlung and cyclotron emission are taken into account. A neutrals model is included, and, in some circumstances, charge-exchange losses are found to exceed all other loss mechanisms. We use the SUNDIALS ARKODE library to solve the underlying equations of this model; the resulting software is suitable for scanning large parameter spaces, and can also be used to model time-dependent phenomena such as a capacitive discharge. MCTrans++ has been used to verify results from prior centrifugal mirrors, create an experimental plan for CMFX and find configurations for future reactor-scale fusion devices.

CONTRIBUTION OF CT ANGIOS IN THE DIAGNOSIS OF SUBRENAL ABDOMINAL AORTA ANEURYSM AT THE LUXEMBOURG MOTHER-CHILD HOSPITAL CENTER

Objective: Our study aimed to study the value of CT angiography in the diagnosis of subrenal abdominal aortic aneurysm at the Mother-Child University Hospital Center Le Luxembourg Methodology : This was a retrospective, descriptive and analytical study carried out over a period of three years (from January 1, 2019 to December 31, 2021) in the radiology departments of CHME Mère et Enfant Le Luxembourg. It concerned all patients who had an angio-CT scan in the radiology department of the CHU-ME Le Luxembourg in whom a subrenal abdominal aortic aneurysm was diagnosed. Excluded from our study were aneurysms of the thoracic aorta and vessels of the neck as well as the limbs. Results : We retained 22 cases of AAA meeting our inclusion criteria. The male gender was the majority (66.7%) with a sex ratio (M/F) of 1.5. The most represented age group was those over 50 with 66.7%. Hypertension was the most represented risk factor with a rate of 33.3%. Abdominal pain was the most frequent functional sign with 77.77%. More than 66.7% of our patients had an abdominal mass. The majority of our patients had a saccular type of aneurysm (67%). The average anteroposterior diameter of the AAA was 56 mm. The average transverse diameter was 63 mm. The average length of the aneurysm was 77 mm. All our patients had heterogeneous aneurysm contents with mural thrombus. The edge of the aneurysm was irregular with loss of parallelism in all our patients. More than half (55.6%) of our patients had aortic calcifications. Only one of our patients presented with fissure syndrome. 33.3% of our patients had the sign of extension to the renal arteries. The majority of our patients had visceral branch patency with a rate of 88.9%. The biological assessment was dominated by anemia with a rate of 44.4%. The echocardium was pathological in 11.1%. Conclusion: Abdominal aortic aneurysms are becoming more and more common. More than 90% of abdominal aortic aneurysms develop at the expense of the infrarenal aorta. The most common vascular risk factors are hypertension and smoking. Aneurysms are generally asymptomatic, making their clinical diagnosis difficult. CT angiography remains the complementary examination of choice in the diagnosis of thoraco-abdominal arterial lesions.

Prediction of absorptivity in Multi-Jet Fusion manufactured polypropylene structures through laser flash and corrected porosity method

For the first time in the literature, this study validates the absorption phenomena in Multi-Jet Fusion (MJF) printed polypropylene (PP) structures through Laser Flash (LFA) and Corrected Porosity (CP) methods. The influence of process parameters such as build height and build orientation was investigated on tensile properties, crystallinity, porosity and thermophysical attributes in MJF printed PP coupons. Results showed that both crystallinity and tensile performance did not significantly vary with either location or build orientation. Interestingly, samples printed in the Z orientation showed a 35% decrease in strain, indicating that Z-oriented MJF coupons were more brittle than the flat samples (XY). Samples printed in Z orientation also possessed higher porosity and relatively lower crystallinity than the XY orientation. However, large deviations within porosity values were an obstacle to determining a suitable build chamber location for manufacturing dense samples. Therefore, a detailed investigation on porosity of printed samples using micro-CT scans and CT image analysis was necessary. Initially, poor contrast was obvious when MJF printed samples were positioned vertically in the micro-CT chamber which was mainly due to high value of horizontal intensity profile (HIP ~ 70%). Contrast in MJF samples improved significantly in the horizontal orientation (HIP ~ 40%). In parallel, the half-time and heat loss were measured in LFA to understand changes in absorption phenomena with height and orientation of the build. A direct correlation was found between LFA half-time and porosity only when the porosity correction method was implemented. Corrected porosity value was found to be inversely proportional to the heat loss of printed PP samples which indicated higher absorption for samples printed in the bottom of build chamber, XY12, whereas lower absorption was observed for less dense Z samples. Finally, heat loss phenomenon was verified using dense reference Pyroceram samples as they possess high diffusivity and low half-time and porosity compared to MJF printed samples. There is a science behind understanding the absorptivity of the MJF process which is related to the complexity of the process and is challenging to address in MJF PP samples when mixed with carbon black. The study showed that accurately determining the level of porosity is the key to validate absorption phenomena within MJF printed coupons. The contributions of this work are the investigation of the light absorption phenomena in MJF printed PP structures, and the establishment of the absorption-porosity correlation. These contributions help to predict the mechanical properties and subsequently the overall quality of the produced parts which can save cost and time in effectively utilising the MJF process.

Structure of the electron temperature profile around the separatrix

The temperature decay length () in the near scrape-off layer (SOL) reflects the ratio between the transport parallel to the magnetic field lines via Spitzer–Härm electron conduction and the perpendicular mechanisms involving neoclassical and anomalous transport. The implementation of the thermal helium beam diagnostic on ASDEX Upgrade has enabled an excellent spatiotemporal study of the structure of the electron temperature profile () around the separatrix and the derivation of the near SOL decay lengths. From the analysis of the profile structure of attached H- and L-mode discharges, a self-consistent correspondence between the extrema of the electron temperature curvature profile () and the position of the separatrix () is revealed. A 1.5 D model for the power balance from closed to open field lines, including the escaping heat flux from the confined region and the parallel losses to the divertor, as well as results from the plasma edge code GRILLIX, support these experimental results. The evaluation shows that the temperature decay length is not constant over the plasma edge and SOL region, so that the absolute value of strongly depends on the analyzed region. Independent of the exact location and in agreement with edge Thomson scattering evaluations, the decay lengths show the known inverse relation to the plasma current ().

A Catastrophic Biodiversity Loss in the Environment Is Being Replicated on the Skin Microbiome: Is This a Major Contributor to the Chronic Disease Epidemic?

There has been a catastrophic loss of biodiversity in ecosystems across the world. A similar crisis has been observed in the human gut microbiome, which has been linked to "all human diseases affecting westernized countries". This is of great importance because chronic diseases are the leading cause of death worldwide and make up 90% of America's healthcare costs. Disease development is complex and multifactorial, but there is one part of the body's interlinked ecosystem that is often overlooked in discussions about whole-body health, and that is the skin microbiome. This is despite it being a crucial part of the immune, endocrine, and nervous systems and being continuously exposed to environmental stressors. Here we show that a parallel biodiversity loss of 30-84% has occurred on the skin of people in the developed world compared to our ancestors. Research has shown that dysbiosis of the skin microbiome has been linked to many common skin diseases and, more recently, that it could even play an active role in the development of a growing number of whole-body health problems, such as food allergies, asthma, cardiovascular diseases, and Parkinson's, traditionally thought unrelated to the skin. Damaged skin is now known to induce systemic inflammation, which is involved in many chronic diseases. We highlight that biodiversity loss is not only a common finding in dysbiotic ecosystems but also a type of dysbiosis. As a result, we make the case that biodiversity loss in the skin microbiome is a major contributor to the chronic disease epidemic. The link between biodiversity loss and dysbiosis forms the basis of this paper's focus on the subject. The key to understanding why biodiversity loss creates an unhealthy system could be highlighted by complex physics. We introduce entropy to help understand why biodiversity has been linked with ecosystem health and stability. Meanwhile, we also introduce ecosystems as being governed by "non-linear physics" principles-including chaos theory-which suggests that every individual part of any system is intrinsically linked and implies any disruption to a small part of the system (skin) could have a significant and unknown effect on overall system health (whole-body health). Recognizing the link between ecosystem health and human health allows us to understand how crucial it could be to maintain biodiversity across systems everywhere, from the macro-environment we inhabit right down to our body's microbiome. Further, in-depth research is needed so we can aid in the treatment of chronic diseases and potentially change how we think about our health. With millions of people currently suffering, research to help mitigate the crisis is of vital importance.

Parallel loss of type VI secretion systems in two multi-drug-resistant Escherichia coli lineages.

The repeated emergence of multi-drug-resistant (MDR) Escherichia coli clones is a threat to public health globally. In recent work, drug-resistant E. coli were shown to be capable of displacing commensal E. coli in the human gut. Given the rapid colonization observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug-resistant E. coli clones. We employed large-scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20 000 genomes representing the full phylogenetic diversity of E. coli. This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterized the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones.

A parallel ensemble optimization and transfer learning based intelligent fault diagnosis framework for bearings

Transfer learning (TL) is an important method to accurately identify the bearing health status in cross-domain and ensure the safe operation of machinery. With the advancement in research, it will become a trend to choose different neural networks or optimization functions to improve and re-model fault diagnosis methods. However, the variants of these fault diagnostic methods are less capable of generalizing input dimensions and do not significantly increase demand for machinery expertise. The idea of ensemble learning solves the problem of low generalization. In this research, a parallel ensemble optimization loss function and multi-source TL based model are proposed to solve the problem of unknown distribution difference between source domain and target domain, thus improving the generalization of optimization objectives. Firstly, based on the signal demodulation method, an adaptive input module is constructed to automatically select the input length from the original vibration signal. Secondly, a TL network with low-dimensional features reuse is constructed to achieve weight and bias sharing. Thirdly, a parallel ensemble optimization loss function is developed to align the data whose distribution is unknown between source and target domains. Finally, two cases with multi-source, unsupervised, and cross-domain TL are used to verify the performance of the proposed method. The average accuracy in case 1 and case 2 is 99.81 % and 99.17 % respectively. It is proved that the proposed method can not only get rid of the limitation of manual input length setting, but also overcome the limitation of optimization function, which is more effective than the existing intelligent fault diagnosis models.

PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response invitro and dramatically improves fibrosis invivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.

Diversification of Ubiquinone Biosynthesis via Gene Duplications, Transfers, Losses, and Parallel Evolution.

The availability of an ever-increasing diversity of prokaryotic genomes and metagenomes represents a major opportunity to understand and decipher the mechanisms behind the functional diversification of microbial biosynthetic pathways. However, it remains unclear to what extent a pathway producing a specific molecule from a specific precursor can diversify. In this study, we focus on the biosynthesis of ubiquinone (UQ), a crucial coenzyme that is central to the bioenergetics and to the functioning of a wide variety of enzymes in Eukarya and Pseudomonadota (a subgroup of the formerly named Proteobacteria). UQ biosynthesis involves three hydroxylation reactions on contiguous carbon atoms. We and others have previously shown that these reactions are catalyzed by different sets of UQ-hydroxylases that belong either to the iron-dependent Coq7 family or to the more widespread flavin monooxygenase (FMO) family. Here, we combine an experimental approach with comparative genomics and phylogenetics to reveal how UQ-hydroxylases evolved different selectivities within the constrained framework of the UQ pathway. It is shown that the UQ-FMOs diversified via at least three duplication events associated with two cases of neofunctionalization and one case of subfunctionalization, leading to six subfamilies with distinct hydroxylation selectivity. We also demonstrate multiple transfers of the UbiM enzyme and the convergent evolution of UQ-FMOs toward the same function, which resulted in two independent losses of the Coq7 ancestral enzyme. Diversification of this crucial biosynthetic pathway has therefore occurred via a combination of parallel evolution, gene duplications, transfers, and losses.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8+ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8+ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX+) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX+ZNF683+CD8+ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103+PD-1+CD8+ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683+CTX+ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683+CTX+ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Parallel Losses of Blue Opsin Correlate with Compensatory Neofunctionalization of UV-Opsin Gene Duplicates in Aphids and Planthoppers.

Expanding on previous efforts to survey the visual opsin repertoires of the Hemiptera, this study confirms that homologs of the UV- and LW-opsin subfamilies are conserved in all Hemiptera, while the B-opsin subfamily is missing from the Heteroptera and subgroups of the Sternorrhyncha and Auchenorrhyncha, i.e., aphids (Aphidoidea) and planthoppers (Fulgoroidea), respectively. Unlike in the Heteroptera, which are characterized by multiple independent expansions of the LW-opsin subfamily, the lack of B-opsin correlates with the presence of tandem-duplicated UV-opsins in aphids and planthoppers. Available data on organismal wavelength sensitivities and retinal gene expression patterns lead to the conclusion that, in both groups, one UV-opsin paralog shifted from ancestral UV peak sensitivity to derived blue sensitivity, likely compensating for the lost B-opsin. Two parallel bona fide tuning site substitutions compare to 18 non-corresponding amino acid replacements in the blue-shifted UV-opsin paralogs of aphids and planthoppers. Most notably, while the aphid blue-shifted UV-opsin clade is characterized by a replacement substitution at one of the best-documented UV/blue tuning sites (Rhodopsin site 90), the planthopper blue-shifted UV-opsin paralogs retained the ancestral lysine at this position. Combined, the new findings identify aphid and planthopper UV-opsins as a new valuable data sample for studying adaptive opsin evolution.