Genome-Wide Analysis of Flax (Linum usitatissimum L.) Growth-Regulating Factor (GRF) Transcription Factors.

Flax is an important cash crop globally with a variety of commercial uses. It has been widely used for fiber, oil, nutrition, feed and in composite materials. Growth regulatory factor (GRF) is a transcription factor family unique to plants, and is involved in regulating many processes of growth and development. Bioinformatics analysis of the GRF family in flax predicted 17 LuGRF genes, which all contained the characteristic QLQ and WRC domains. Equally, 15 of 17 LuGRFs (88%) are predicted to be regulated by lus-miR396 miRNA. Phylogenetic analysis of GRFs from flax and several other well-characterized species defined five clades; LuGRF genes were found in four clades. Most LuGRF gene promoters contained cis-regulatory elements known to be responsive to hormones and stress. The chromosomal locations and collinearity of LuGRF genes were also analyzed. The three-dimensional structure of LuGRF proteins was predicted using homology modeling. The transcript expression data indicated that most LuGRF family members were highly expressed in flax fruit and embryos, whereas LuGRF3, LuGRF12 and LuGRF16 were enriched in response to salt stress. Real-time quantitative fluorescent PCR (qRT-PCR) showed that both LuGRF1 and LuGRF11 were up-regulated under ABA and MeJA stimuli, indicating that these genes were involved in defense. LuGRF1 was demonstrated to be localized to the nucleus as expected for a transcription factor. These results provide a basis for further exploration of the molecular mechanism of LuGRF gene function and obtaining improved flax breeding lines.

Maize plant architecture trait QTL mapping and candidate gene identification based on multiple environments and double populations.

BACKGROUND: The plant architecture traits of maize determine the yield. Plant height, ear position, leaf angle above the primary ear and internode length above the primary ear together determine the canopy structure and photosynthetic efficiency of maize and at the same time affect lodging and disease resistance. A flat and tall plant architecture confers an obvious advantage in the yield of a single plant but is not conducive to dense planting and results in high rates of lodging; thus, it has been gradually eliminated in production. Although using plants that are too compact, short and density tolerant can increase the yield per unit area to a certain extent, the photosynthetic efficiency of such plants is low, ultimately limiting yield increases. Genetic mapping is an effective method for the improvement of plant architecture to identify candidate genes for regulating plant architecture traits. RESULTS: To find the best balance between the yield per plant and the yield per unit area of maize, in this study, the F2:3 pedigree population and a RIL population with the same male parent were used to identify QTL for plant height (PH), ear height (EH), leaf angle and internode length above the primary ear (LAE and ILE) in Changchun and Gongzhuling for 5 consecutive years (2016-2020). A total of 11, 13, 23 and 13 QTL were identified for PH, EH, LAE, and ILE, respectively. A pleiotropic consistent QTL for PH overlapped with that for EH on chromosome 3, with a phenotypic variation explanation rate from 6.809% to 21.96%. In addition, there were major consistent QTL for LAE and ILE, and the maximum phenotypic contribution rates were 24.226% and 30.748%, respectively. Three candidate genes were mined from the three consistent QTL regions and were involved in the gibberellin-activated signal pathway, brassinolide signal transduction pathway and auxin-activated signal pathway, respectively. Analysis of the expression levels of the three genes showed that they were actively expressed during the jointing stage of vigorous maize growth. CONCLUSIONS: In this study, three consistent major QTL related to plant type traits were identified and three candidate genes were screened. These results lay a foundation for the cloning of related functional genes and marker-assisted breeding of related functional genes.

Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD).

We previously described the discovery of a novel indole series compounds as oral SERD for ER positive breast cancer treatment. Further SAR exploration focusing on substitutions on indole moiety of compound 12 led to the discovery of a clinical candidate LX-039. We report herein its profound anti-tumor activity, desirable ER antagonistic characteristics combined with favorable pharmacokinetic and preliminary safety properties. LX-039 is currently in clinical trial (NCT04097756).

Design, syntheses and evaluations of novel indole derivatives as orally selective estrogen receptor degraders (SERD).

Most estrogen receptor positive (ER +) breast cancers depend on ER signaling pathway to develop. Clinical application of SERD fulvestrant effectively degraded ER, blocked its function and prolonged progression free survival of ER + breast cancer patients. However, current SERD suffers from limited bioavailability, therefore is given as intramuscular (IM) injection. In this paper, we report herein a novel indole series compounds with nanomolar range ER degradation potencies and oral systemic exposures. Selected compounds suppressed tumor growth in vivo in ER + MCF7 breast cancer CDX model via p.o. administration. All those data supported further optimizations of this analog to develop preclinical candidate as oral SERD for ER + breast cancer's treatment.

Chemical synthesis of tetracyclic terpenes and evaluation of antagonistic activity on endothelin-A receptors and voltage-gated calcium channels.

A class of tetracyclic terpenes was synthesized and evaluated for antagonistic activity of endothelin-1 (ET-1) induced vasoconstriction and inhibitory activity of voltage-activated Ca(2+) channels. Three repeated Robinson annulation reactions were utilized to construct the tetracyclic molecules. A stereoselective reductive Robinson annulation was discovered for the formation of optically pure tricyclic terpenes. Stereoselective addition of cyanide to the hindered α-face of tetracyclic enone (-)-18 was found and subsequent transformation into the aldehyde function was affected by the formation of bicyclic hemiiminal (-)-4. Six selected synthetic tetracyclic terpenes show inhibitory activities in ET-1 induced vasoconstriction in the gerbil spiral modiolar artery with putative affinity constants ranging between 93 and 319 nM. Moreover, one compound, (-)-3, was evaluated further and found to inhibit voltage-activated Ca(2+) currents but not to affect Na(+) or K(+) currents in dorsal root ganglion cells under similar concentrations. These observations imply a dual mechanism of action. In conclusion, tetracyclic terpenes represent a new class of hit molecules for the discovery of new drugs for the treatment of pulmonary hypertension and vascular related diseases.

Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3ß of substituted quinolines.

A new series of fifteen 5-, 6-, and 8-appended 4-methylquinolines were synthesized and evaluated for their neural protective activities. Selected compounds were further examined for their inhibition of glycogen synthase kinase-3ß (GSK-3ß) and protein kinase C (PKC). Two most potent analogs, compounds 3 and 10, show nanomolar protective activities in amyloid ß-induced MC65 cells and enzymatic inhibitory activities against GSK-3ß, but poor PKC inhibitory activities. Using normal mouse model, the distribution of the most potent analog 3 in various tissues and possible toxic effects in the locomotors and inhibition of liver transaminases activities were carried out. No apparent decline of locomotor activity and no inhibition of liver transaminases were found. The compound appears to be safe for long-term use in Alzheimer's disease mouse model.

Modulation of Point Spread Function for Super-Resolution Imaging.

High image resolution is desired in wave-related areas such as ultrasound, acoustics, optics, and electromagnetics. However, the spatial resolution of an imaging system is limited by the spatial frequency of the point spread function (PSF) of the system due to diffraction. In this article, the PSF is modulated in amplitude, phase, or both to increase the spatial frequency to reconstruct super-resolution images of objects or wave sources/fields, where the modulator can be a focused shear wave produced remotely by, for example, a radiation force from a focused Bessel beam or X-wave, or can be a small particle manipulated remotely by a radiation-force (such as acoustic and optical tweezers) or electrical and magnetic forces. A theory of the PSF-modulation method was developed, and computer simulations and experiments were conducted. The result of an ultrasound experiment shows that a pulse-echo (two-way) image reconstructed has a super-resolution (0.65 mm) as compared to the diffraction limit (2.65 mm) using a 0.5-mm-diameter modulator at 1.483-mm wavelength, and the signal-to-noise ratio (SNR) of the image was about 31 dB. If the minimal SNR of a "visible" image is 3, the resolution can be further increased to about 0.19 mm by decreasing the size of the modulator. Another ultrasound experiment shows that a wave source was imaged (one-way) at about 30-dB SNR using the same modulator size and wavelength above. The image clearly separated two 0.5-mm spaced lines, which gives a 7.26-fold higher resolution than that of the diffraction limit (3.63 mm). Although, in theory, the method has no limit on the highest achievable image resolution, in practice, the resolution is limited by noises. Also, a PSF-weighted super-resolution imaging method based on the PSF-modulation method was developed. This method is easier to implement but may have some limitations. Finally, the methods above can be applied to imaging systems of an arbitrary PSF and can produce 4-D super-resolution images. With a proper choice of a modulator (e.g., a quantum dot) and imaging system, nanoscale (a few nanometers) imaging is possible.

Oxidation behavior and performance deterioration of cracking furnace tubes in service.

In recent years, the centrifugal casting material Cr35Ni45Nb has been widely used in cracking furnace tubes. The common failure forms in the service process are carburizing cracking, bending, bulging, creep cracking, thermal fatigue cracking, thermal shock cracking, and oxidation, among which the inner wall oxidation and carburization of cracking furnace tubes cause the largest proportion of material failure. In this paper, we will discuss the inner wall oxidation behavior of cracking furnace tubes and its influence on the lasting strength of the furnace tubes. Several groups of endurance tests were designed for service furnace tubes, and the oxidation characteristics, oxide film rupture damage, and its influence on the endurance life of furnace tubes in different service times were analyzed by means of XRD, SEM, and so on. The results show that the oxide layer of the furnace tube is divided into two layers, the outer layer is repeatedly destroyed and rebuilt. With the continuous evolution of material structure, its properties also deteriorate, and its tensile strength, yield strength, elongation, and durable life all decrease significantly.

Cloning and functional analysis of ZmMADS42 gene in maize.

Maize (Zea mays L.) is the most important cereal crop in the world. Flowering period and photoperiod play important roles in the reproductive development of maize. This study, investigated ZmMADS42, a gene that is highly expressed in the shoot apical meristem. Agrobacterium infection was used to successfully obtain overexpressed ZmMADS42 plants. Fluorescence quantitative PCR revealed that the expression of the ZmMADS42 gene in the shoot apical meristem of transgenic plants was 2.8 times higher than that of the wild-type(WT). In addition, the expression of the ZmMADS42 gene in the endosperm was 2.4 times higher than that in the wild-type. The seed width of the T2 generation increased by 5.35%, whereas the seed length decreased by 7.78% compared with that of the wild-type. Dissection of the shoot tips of transgenic and wild-type plants from the 7-leaf stage to the 9-leaf stage revealed that the transgenic plants entered the differentiation stage earlier and exhibited more tassel meristems during their vegetative growth period. The mature transgenic plants were approximately 20 cm shorter in height and had a lower panicle position than the wild-type plants. Comparing the flowering period, the tasseling, powdering, and silking stages of the transgenic plants occurred 10 days earlier than those of the wild-type plants. The results showed that the ZmMADS42 gene played a significant role in regulating the flowering period and plant height of maize.

A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort.

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

GL-FusionNet: Fusing global and local features to classify deep and superficial partial thickness burn.

Burns constitute one of the most common injuries in the world, and they can be very painful for the patient. Especially in the judgment of superficial partial thickness burns and deep partial thickness burns, many inexperienced clinicians are easily confused. Therefore, in order to make burn depth classification automated as well as accurate, we have introduced the deep learning method. This methodology uses a U-Net to segment burn wounds. On this basis, a new thickness burn classification model that fuses global and local features (GL-FusionNet) is proposed. For the thickness burn classification model, we use a ResNet50 to extract local features, use a ResNet101 to extract global features, and finally implement the add method to perform feature fusion and obtain the deep partial or superficial partial thickness burn classification results. Burns images are collected clinically, and they are segmented and labeled by professional physicians. Among the segmentation methods, the U-Net used achieved a Dice score of 85.352 and IoU score of 83.916, which are the best results among all of the comparative experiments. In the classification model, different existing classification networks are mainly used, as well as a fusion strategy and feature extraction method that are adjusted to conduct experiments; the proposed fusion network model also achieved the best results. Our method yielded the following: accuracy of 93.523, recall of 93.67, precision of 93.51, and F1-score of 93.513. In addition, the proposed method can quickly complete the auxiliary diagnosis of the wound in the clinic, which can greatly improve the efficiency of the initial diagnosis of burns and the nursing care of clinical medical staff.

Ultrasound Concave 2-D Ring Array for Retinal Stimulation.

An ultrasound concave 2-D ring array transducer was designed for applications in visual stimulation of the retina with a long-term goal to restore vision in individuals with intact neurons but suffering blindness due to retinopathies. The array was synthesized and has a frequency of 20 MHz (0.075-mm wavelengths in water), 18-mm focal length (the curvature of the concave array), 1004 elements (with a pitch of 4.0 wavelengths), and inner and outer diameters of 9 and 14 mm, respectively. Wave patterns produced with the array at the focal distance were simulated. Results show that the wave patterns obtained can achieve a full-width-at-half-maximum (FWHM) resolution of 0.147 mm that is very close to the FWHM diffraction limit (0.136 mm). In addition, a scaled experiment at a lower frequency of 2.5 MHz was performed. The result is very close to those obtained with the simulations.

Some thoughts on integrity management of mounded storage tanks.

In the domestic petrochemical industry, mounded storage tanks (MSTs) are widely used to store hazardous chemicals. The shell of the mounded storage tank is completely covered by soil to effectively mitigate the effect of the external environment and prevent thermal-expansion-induced explosion of the stored material. Because mounded storage tanks are mostly underground, they are highly safe, provide effective land utilization, and are highly energy efficient. Furthermore, the impact radius in case of an explosion is less than that of aboveground tanks. However, adequate regulations and standards for safety management are yet to be established. This study established a novel method for the integrity management of mounded storage tanks through database construction, risk assessment, applicability monitoring, and testing. At the same time, the risk assessment method for mounded storage tank characteristics is constructed for the first time.

JAM-A Overexpression in Human Umbilical Cord-Derived Mesenchymal Stem Cells Accelerated the Angiogenesis of Diabetic Wound By Enhancing Both Paracrine Function and Survival of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) is promising in promoting wound healing mainly due to their paracrine function. Nonetheless, the transplanted MSCs presented poor survival with cell dysfunction and paracrine problem in diabetic environment, thus limiting their therapeutic efficacy and clinical application. JAM-A, an adhesion molecule, has been reported to play multi-functional roles in diverse cells. We therefore investigated the potential effect of JAM-A on MSCs under diabetic environment and explored the underlying mechanism. Indeed, high-glucose condition inhibited MSCs viability and JAM-A expression. However, JAM-A abnormality was rescued by lentivirus transfection and JAM-A overexpression promoted MSCs proliferation, migration and adhesion under hyperglycemia. Moreover, JAM-A overexpression attenuated high-glucose-induced ROS production and MSCs apoptosis. The bio-effects of JAM-A on MSCs under hyperglycemia were confirmed by RNA-seq with enrichment analyses. Moreover, Luminex chip results showed JAM-A overexpression dramatically upregulated PDGF-BB and VEGF in the supernatant of MSCs, which was verified by RT-qPCR and western blotting. The supernatant was further found to facilitate HUVECs proliferation, migration and angiogenesis under hyperglycemia. In vivo experiments revealed JAM-A overexpression significantly enhanced MSCs survival, promoted wound angiogenesis, and thus accelerated diabetic wound closure, partially by enhancing PDGF-BB and VEGF expression. This study firstly demonstrated that JAM-A expression of MSCs was inhibited upon high-glucose stimulation. JAM-A overexpression alleviated high-glucose-induced MSCs dysfunction, enhanced their anti-oxidative capability, protected MSCs from hyperglycemia-induced apoptosis and improved their survival, thus strengthening MSCs paracrine function to promote angiogenesis and significantly accelerating diabetic wound healing, which offers a promising strategy to maximize MSCs-based therapy in diabetic wound.

Mapping intellectual structure and research hotspots in the field of fibroblast-associated DFUs: a bibliometric analysis.

Background: Diabetic foot ulcers (DFUs) are one of the most popular and severe complications of diabetes. The persistent non-healing of DFUs may eventually contribute to severe complications such as amputation, which presents patients with significant physical and psychological challenges. Fibroblasts are critical cells in wound healing and perform essential roles in all phases of wound healing. In diabetic foot patients, the disruption of fibroblast function exacerbates the non-healing of the wound. This study aimed to summarize the hotspots and evaluate the global research trends on fibroblast-related DFUs through bibliometric analysis. Methods: Scientific publications on the study of fibroblast-related DFUs from January 1, 2000 to April 27, 2022 were retrieved from the Web of Science Core Collection (WoSCC). Biblioshiny software was primarily performed for the visual analysis of the literature, CiteSpace software and VOSviewer software were used to validate the results. Results: A total of 479 articles on fibroblast-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were the USA, The Chinese University of Hong Kong, Wound Repair and Regeneration, and Seung-Kyu Han. In addition, keyword co-occurrence networks, historical direct citation networks, thematic map, and the trend topics map summarize the research hotspots and trends in this field. Conclusion: Current studies indicated that research on fibroblast-related DFUs is attracting increasing concern and have clinical implications. The cellular and molecular mechanisms of the DFU pathophysiological process, the molecular mechanisms and therapeutic targets associated with DFUs angiogenesis, and the measures to promote DFUs wound healing are three worthy research hotspots in this field.

Sequencing technology as a major impetus in the advancement of studies into rheumatism: A bibliometric study.

Background: Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism. Methods: Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science™ (Clarivate™, Philadelphia, PA, USA) database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words. Results: The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research. Conclusions: Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers.

A bibliometric analysis of the role of microbiota in trauma.

Introduction: Over the last several decades, the gut microbiota has been implicated in the formation and stabilization of health, as well as the development of disease. With basic and clinical experiments, scholars are gradually understanding the important role of gut microbiota in trauma, which may offer novel ideas of treatment for trauma patients. In this study, we purposed to summarize the current state and access future trends in gut microbiota and trauma research. Methods: We retrieved relevant documents and their published information from the Web of Science Core Collection (WoSCC). Bibliometrix package was responsible for the visualized analysis. Results: Totally, 625 documents were collected and the number of annual publications kept increasing, especially from 2016. China published the most documents while the USA had the highest local citations. The University of Colorado and Food & Function are respectively the top productive institution and journal, as PLOS One is the most local cited journal. With the maximum number of articles and local citations, Deitch EA is supported to be the most contributive author. Combining visualized analysis of keywords and documents and literature reading, we recognized two key topics: bacteria translocation in trauma and gut microbiota's effect on inflammation in injury, especially in nervous system injury. Discussion: The impact of gut microbiota on molecular and pathological mechanism of inflammation is the focus now. In addition, the experiments of novel therapies based on gut microbiota's impact on trauma are being carried out. We hope that this study can offer a birds-eye view of this field and promote the gradual improvement of it.

Tracing the evolving dynamics and research hotspots of microbiota and immune microenvironment from the past to the new era.

Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like the inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. This article aims to review the documents in this field and summarize the research hotspots as well as developing processes. Gut microbiota and immune microenvironment-related documents from 1976 to 2022 were obtained from the Web of Science Core Collection database. Bibliometrics was used to assess the core authors and journals, most contributive countries and affiliations together with hotspots in this field and keyword co-occurrence analysis. Data were visualized to help comprehension. Nine hundred and twelve documents about gut microbiota and immune microenvironment were retrieved, and the annual publications increased gradually. The most productive author, country, and affiliation were "Zitvogel L," USA and "UNIV TEXAS MD ANDERSON CANC CTR," respectively. FRONTIERS IN IMMUNOLOGY, CANCERS, and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE were the periodicals with most publications. Keyword co-occurrence analysis identified three clusters, including gut microbiota, inflammation, and IBD. Combined with the visualized analysis of documents and keyword co-occurrence as well as literature reading, we recognized three key topics of gut microbiota: cancer and therapy; immunity, inflammation and IBD; acute injuries and metabolic diseases. This article revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.IMPORTANCEGut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. While the application of bibliometrics in the field of gut microbiota and immune microenvironment still remains blank, which focused more on the regulation of the gut microbiota on the immune microenvironment of different kinds of diseases. Here, we intended to review and summarize the presented documents in gut microbiota and immune microenvironment field by bibliometrics. And we revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.

Synthesis and anti-norovirus activity of pyranobenzopyrone compounds.

During the last decade, noroviruses have gained media attention as the cause of large scale outbreaks of gastroenteritis on cruise ships, dormitories, nursing homes, etc. Although noroviruses do not multiply in food or water, they can cause large outbreaks because approximately 10-100 virions are sufficient to cause illness in a healthy adult. Recently, it was shown that the activity of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) enzyme may be important in norovirus infection. In search of anti-noroviral agents based on the inhibition of ACAT1, we synthesized and evaluated the inhibitory activities of a class of pyranobenzopyrone molecules containing amino, pyridine, substituted quinolines, or 7,8-benzoquinoline nucleus. Three of the sixteen evaluated compounds possess ED(50) values in the low micrometer range. 2-Quinolylmethyl derivative 3A and 4-quinolylmethyl derivative 4A showed ED(50) values of 3.4 and 2.4 µM and TD(50) values of >200 and 96.4 µM, respectively. The identified active compounds are suitable for further modification for the development of anti-norovirus agents.

Causal contribution of optic flow signal in Macaque extrastriate visual cortex for roll perception.

Optic flow is a powerful cue for inferring self-motion status which is critical for postural control, spatial orientation, locomotion and navigation. In primates, neurons in extrastriate visual cortex (MSTd) are predominantly modulated by high-order optic flow patterns (e.g., spiral), yet a functional link to direct perception is lacking. Here, we applied electrical microstimulation to selectively manipulate population of MSTd neurons while macaques discriminated direction of rotation around line-of-sight (roll) or direction of linear-translation (heading), two tasks which were orthogonal in 3D spiral coordinate using a four-alternative-forced-choice paradigm. Microstimulation frequently biased animal's roll perception towards coded labeled-lines of the artificial-stimulated neurons in either context with spiral or pure-rotation stimuli. Choice frequency was also altered between roll and translation flow-pattern. Our results provide direct causal-link evidence supporting that roll signals in MSTd, despite often mixed with translation signals, can be extracted by downstream areas for perception of rotation relative to gravity-vertical.