bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of BraRGL1 in regulation of Brassica rapa bolting and flowering
Authors: Wang Yudan , Song Shiwei , Hao Yanwei , Chen Changming , Ou Xi , He Bin , Zhang Jiewen , Jiang Zhehao , Li Chengming , Zhang Shuaiwei , Su Wei , Chen Riyuan
Published: June 2023

Gibberellin (GA) plays a major role in controlling Brassica rapa stalk development. As an essential negative regulator of GA signal transduction, DELLA proteins may exert significant effects on stalk development. However, the regulatory mechanisms underlying this regulation remain unclear. In this study, we report highly efficient and inheritable mutagenesis using the CRISPR/Cas9 gene editing system in BraPDS (phytoene desaturase) and BraRGL1 (key DELLA protein) genes. We observed a loss-of-function mutation in BraRGL1 due to two amino acids in GRAS domain. The flower bud differentiation and bolting time of BraRGL1 mutants were significantly advanced. The expression of GA-regulatory protein (BraGASA6), flowering related genes (BraSOC1, BraLFY), expansion protein (BraEXPA11) and xyloglucan endotransferase (BraXTH3) genes was also significantly upregulated in these mutants. BraRGL1-overexpressing plants displayed the contrasting phenotypes. BraRGL1 mutants were more sensitive to GA signaling. BraRGL1 interacted with BraSOC1, and the interaction intensity decreased after GA3 treatment. In addition, BraRGL1 inhibited the transcription-activation ability of BraSOC1 for BraXTH3 and BraLFY genes, but the presence of GA3 enhanced the activation ability of BraSOC1, suggesting that the BraRGL1-BraSOC1 module regulates bolting and flowering of B. rapa through GA signal transduction. Thus, we hypothesized that BraRGL1 is degraded, and BraSOC1 is released in the presence of GA3, which promotes the expression of BraXTH3 and BraLFY, thereby inducing stalk development in B. rapa. Further, the BraRGL1-M mutant promoted the flower bud differentiation without affecting the stalk quality. Thus, BraRGL1 can serve as a valuable target for the molecular breeding of early maturing varieties.
Interlacing in Atomic Resolution Scanning Transmission Electron Microscopy
Authors: Peters Jonathan J P , Mullarkey Tiarnan , Gott James A , Nelson Elizabeth , Jones Lewys
Published: June 2023

Fast frame rates are desirable in scanning transmission electron microscopy for a number of reasons: controlling electron beam dose, capturing in situ events, or reducing the appearance of scan distortions. While several strategies exist for increasing frame rates, many impact image quality or require investment in advanced scan hardware. Here, we present an interlaced imaging approach to achieve minimal loss of image quality with faster frame rates that can be implemented on many existing scan controllers. We further demonstrate that our interlacing approach provides the best possible strain precision for a given electron dose compared with other contemporary approaches.
Presentation, treatment, and outcomes of unifocal and multifocal osseous vertebral Langerhans cell histiocytosis lesions in patients under 18 years old
Authors: Ezeokoli Ekene U. , Smith Tyler , Mitchell Parker , Schlehr Eva , Borici Neritan , Montgomery Nicole
Published: June 2023

This study aims to (1) clinically and radiographically characterize a series of unifocal (single-system single-site) and multifocal (single-system multiple-site) langerhans cell histiocytosis (LCH) lesions in the vertebra and (2) determine the success and recurrence rates with different treatment modalities in a pediatric population at a tertiary children’s hospital. Patients younger than 18 years old with a diagnosis of LCH before 1 June 2021 at our institution were reviewed. The inclusion criteria were a unifocal or multifocal vertebral lesion without systemic disease. Clinical presentations, lesion sites, radiographic findings, treatments, complications, recurrence rates, and length of follow-up were reviewed and recorded. Thirty-nine patients had unifocal (36%) or multifocal (64%) vertebral lesions. 44% of patients had vertebral lesions only. The most common clinical presentation was neck or back pain (51%) and difficulty or inability to ambulate (15%). 70 vertebrae were involved in total; 59% cervical, 62% thoracic, 49% lumbar, and 10% sacral. 88% of multifocal patients underwent chemotherapy compared to 60% of unifocal patients. The recurrence rate in the entire cohort was 10%. The median length of follow-up was 5.2 years (0.6–16.8). Chemotherapy is often utilized as a treatment for vertebral LCH lesions regardless of unifocal or multifocal osseous presentation, with good outcomes and low recurrence rates. However other treatments such as observation only and steroid injections may be a better option with smaller and less widespread lesions due to side effects and length of treatment with chemotherapy. Determination of more invasive treatments including surgical excision or fixation will need to be considered on a case-by-case basis. Level of evidence: IV.
Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer
Authors: Liu Huiping , Zhou Ling , Cheng Hongyan , Wang Shang , Luan Wenqing , Cai E , Ye Xue , Zhu Honglan , Cui Heng , Li Yi , Chang Xiaohong
Published: June 2023

Background:

High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.

Methods:

Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages.

Results:

Fourteen DEGs, ADIPOQ, ALPK2, BARX1, CD37, CNR2, COL5A3, FABP4, FAP, GPR68, ITGBL1, MOXD1, PODNL1, SFRP2, and TRAF3IP3, were upregulated in metastatic tumors in every database while CADPS, GATA4, STAR, and TSPAN8 were downregulated. ALPK2, FAP, SFRP2, GATA4, STAR, and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC (P = 0.0002 and P = 0.0001, respectively).

Conclusions:

This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2, which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Surgical Treatment of Ischial Ulcers Associated with Deposition of β2-Microglobulin in Two Cases of Dialysis-related Amyloidosis
Authors: Fujita Tamaki , Hasegawa Yuuki , Osa Nagisa , Niimi Yosuke , Sakurai Hiroyuki
Published: June 2023

The accumulation of β2-microglobulin due to long-term hemodialysis is known as dialysis-related amyloidosis, a rare phenomenon that manifests as a subcutaneous mass. Subcutaneous β2-microglobulin amyloidomas are predominantly located on the buttocks. Owing to the load-bearing properties of this location and proximity to the anus, amyloidomas on the buttocks may be prone to pressure ulcers and infection. This report presents two cases of long-term hemodialysis patients who required surgical treatment for infected ulcers caused by buttock amyloidomas. In the first case, treatment failed after the amyloidoma was excised and covered with a single-stage skin flap. In the second case, successful treatment was accomplished by reducing the volume of the amyloidoma, followed by a pause to allow for granulation growth and a two-stage skin graft. Amyloids of this nature are known to be cytotoxic; thus, a robust wound preparation technique should be used until the excision site is fully covered with granulation tissue before wound closure is initiated at the time of surgery. In addition, buttock amyloidomas often extend subcutaneously through the hip joint, and repeated infections may lead to more severe outcomes, such as hip joint infections. The number of dialysis-related amyloidosis patients has been increasing in recent years; thus, we report these case studies to improve patient outcomes in similar cases.
Prediction of long-term survival among patients with cirrhosis using time-varying models
Authors: Goldberg David , Zarnegarnia Yalda
Published: June 2023

Background:

Risk prediction among patients with cirrhosis has historically focused on short-term (ie, 90 days) mortality among patients waitlisted for a transplant. Although several models have been developed to predict intermediate and longer term survivals, they have important limitations, namely, including only baseline laboratory and clinical variables to predict survival over a time horizon of years.

Methods:

We developed prediction models using time-varying laboratory and clinical data among patients with cirrhosis in the OneFlorida Clinical Research Consortium. We fit extended Cox models and assessed model discrimination and calibration in complete-case analysis and imputation of missing laboratory data.

Results:

Among 15,277 patients, 9922 (64.9%) were included in the complete-case analysis. Final models included demographic (age and sex), time-updating laboratory (albumin, alanine transaminase, alkaline phosphatase, bilirubin, platelet, and sodium), and time-updating clinical (ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and bleeding esophageal varices) variables. Model discrimination was excellent in the complete-case analysis [AUC and concordance-index (C-index) > 0.85] at 1-, 2-, 3-, 4-, and 5-year time points. Model performance was unchanged with the exclusion of race and ethnicity as model predictors. Model discrimination was excellent (C-index >0.8) when imputation was used for patients with 1 or 2 missing laboratory variables.

Discussion:

Using data from a statewide sample of patients with cirrhosis, we developed and internally validated a time-updating model to predict survival with excellent discrimination. Based on its measures of discrimination (AUC and c-index), this model matched or exceeded the performance of other published risk models depending on the time horizon. If externally validated, this risk score could improve the care of patients with cirrhosis by improving counseling on intermediate and longer term outcomes to guide clinical decision-making and advanced care planning.
Exosome-associated lysophosphatidic acid signaling contributes to cancer pain
Authors: Khasabova Iryna A. , Khasabov Sergey G. , Johns Malcolm , Juliette Joe , Zheng Aunika , Morgan Hannah , Flippen Alyssa , Allen Kaje , Golovko Mikhail Y. , Golovko Svetlana A. , Zhang Wei , Marti James , Cain David , Seybold Virginia S. , Simone Donald A.
Published: June 2023

Pain associated with bone cancer remains poorly managed, and chemotherapeutic drugs used to treat cancer usually increase pain. The discovery of dual-acting drugs that reduce cancer and produce analgesia is an optimal approach. The mechanisms underlying bone cancer pain involve interactions between cancer cells and nociceptive neurons. We demonstrated that fibrosarcoma cells express high levels of autotaxin (ATX), the enzyme synthetizing lysophosphatidic acid (LPA). Lysophosphatidic acid increased proliferation of fibrosarcoma cells in vitro. Lysophosphatidic acid is also a pain-signaling molecule, which activates LPA receptors (LPARs) located on nociceptive neurons and satellite cells in dorsal root ganglia. We therefore investigated the contribution of the ATX–LPA–LPAR signaling to pain in a mouse model of bone cancer pain in which fibrosarcoma cells are implanted into and around the calcaneus bone, resulting in tumor growth and hypersensitivity. LPA was elevated in serum of tumor-bearing mice, and blockade of ATX or LPAR reduced tumor-evoked hypersensitivity. Because cancer cell–secreted exosomes contribute to hypersensitivity and ATX is bound to exosomes, we determined the role of exosome-associated ATX–LPA–LPAR signaling in hypersensitivity produced by cancer exosomes. Intraplantar injection of cancer exosomes into naive mice produced hypersensitivity by sensitizing C-fiber nociceptors. Inhibition of ATX or blockade of LPAR attenuated cancer exosome-evoked hypersensitivity in an ATX–LPA–LPAR-dependent manner. Parallel in vitro studies revealed the involvement of ATX–LPA–LPAR signaling in direct sensitization of dorsal root ganglion neurons by cancer exosomes. Thus, our study identified a cancer exosome-mediated pathway, which may represent a therapeutic target for treating tumor growth and pain in patients with bone cancer.
Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation
Authors: Wang Melinda , Ge Jin , Ha Nghiem , Shui Amy M. , Huang Chiung-Yu , Cullaro Giuseppe , Lai Jennifer C.
Published: June 2023

Goals:

We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival.

Background:

The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time.

Study:

We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions.

Results:

Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival (P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients (P = 0.30).

Conclusions:

While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.
Endoscopic Balloon Dilatation-Based Membrane Resection for Membranous Duodenal Stenosis: A Feasibility and Safety Study (With Video)
Authors: Wang Xing , Lin Kai , Liu Haifeng , Hu Zhihong , Ye Guogang , Sheng Qingfeng , Lv Zhibao
Published: June 2023

Objectives:

Surgery is generally considered as the first-line therapy for membranous duodenal stenosis (MDS) in children. However, abdominal surgery leaves permanent scars and may even cause intestinal adhesion. Therefore, an effective, safe, and minimally invasive method is urgently needed. This study aimed to evaluate the safety, efficacy, and feasibility of endoscopic balloon dilatation-based membrane resection (EBD-MR) to treat MDS in children.

Methods:

We retrospectively reviewed patients with MDS treated with EBD-MR in Shanghai Children’s Hospital from May 2016 to August 2021. Primary study outcome was clinical success, defined as weight gain and complete remission of vomiting, without the need for repeat endoscopic or surgical intervention during follow-up. Secondary outcomes included technical success, diameter changes of the membrane opening, and adverse events.

Results:

Nineteen children (9 females, mean age 14.5 ± 11.2 months) received endoscopic treatment for MDS, and clinical success was achieved in 18 of 19 patients (94.7%). No bleeding, perforation, and jaundice occurred. Diameters of the membrane opening increased from 2.97 ± 2.87 mm to 9.78 ± 1.27 mm after the treatment, symptoms of vomiting did not reappear during 10–73 months of follow-up, and body mass index of the children increased from 14.9 ± 2.2 kg/m2 (pre-operation) to 16.2 ± 3.7 kg/m2 (6 months after operation). One patient required surgical revision because of existence of a second web; three patients received 2–3 sessions of endoscopic treatment to obtain the final remission.

Conclusions:

The EBD-MR technique is safe, effective, and feasible for MDS, which provided an excellent alternative to surgical management for the disease in pediatric patients.
PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Authors: Awad Heyam A. , Sughayer Maher A. , Obeid Jumana M. , Heilat Yaqoot N. , Alhesa Ahmad S. , Yousef Reda M. , Hasasna Nabil M. , Masoud Shafiq A. , Saleh Tareq
Published: June 2023

Anti–programmed death-ligand 1 (PD-L1) treatments can improve colorectal carcinoma (CRC) survival; however, there is still controversy regarding the relationship between PD-L1 expression and the outcome of immunotherapeutic treatment and survival. The discrepancies are partly caused by the lack of a unified scoring system. This retrospective, cross-sectional study evaluated PD-L1 by immunohistochemistry in 127 CRC cases and compared the 3 scoring systems used to assess PD-L1: Tumor Percentage Score (TPS), Combined Positive Score (CPS), and immune cell (IC) score. Correlations were calculated using the χ2 test. Kaplan-Meier curves with the Log-rank test were used to measure the contribution of PD-L1 expression to survival. PD-L1-positive rate were 29.9%, 57.5%, and 55.9% based on TPS, CPS, and IC score, respectively. TPS showed a better correlation with the clinicopathologic features being significantly higher with young age, T4, and adenocarcinomas (compared with mucinous/signet ring). TPS also showed an increasing trend with higher grade, lymph node stage, and male sex, although these variables were not significantly associated with PD-L1 expression. There was no correlation between PD-L1 expression and mismatch repair protein status in the 3 scoring methods. The probability of survival was higher for PD-L1-negative cases in the first 60 months after surgery if scored by the TPS method (P=0.058). Future efforts correlating PD-L1 status with response to treatment are needed to decide on the best scoring method to be used for making therapy decisions.
Partly cystic common peroneal nerve schwannoma: an unusual cause of hallux drop
Authors: Mishra Abhishek , Kumar Naresh , Singh Simarjeet
Published: June 2023

Traumatic peroneal nerve injury is the usual underlying cause for foot drop. Other causes are like neoplastic, metabolic, or infective are rarely seen. We are reporting an extremely rare case of peroneal neuropathy due to a partly cystic schwannoma of common peroneal nerve leading to hallux drop.
Survey of global health education in physical medicine and rehabilitation residency programs across the United States
Authors: Petriello Marla , Mathews Amy , Eison Kaile , Hartman Elana , Steere Hannah
Published: June 2023

The need for global rehabilitation as well as the interest of medical trainees in global health education is rising. Physical medicine and rehabilitation (PM&R) physicians and trainees are trained to care for people with disabilities. Our objectives were to (1) quantify the interest, access, and type of global health education currently available for US PM&R residents and fellows, (2) determine the rehabilitation-specific topics, amount of time, and learning formats preferred by PM&R residents and fellows in developing a global health education course, and (3) determine the barriers to incorporating these global health experiences perceived by both trainees and program directors (PDs), as well as PD support for global health education for trainees. Two cross-sectional surveys created via REDCap software were administered to PM&R residents and fellows and to PDs. Responses from 96 residents and fellows (maximum N=1505) and 40 PDs (maximum N=105) were recorded. A total of 32.2% of trainees and 27.5% of PDs reported global health training was currently available in their program. Global health-specific didactic lectures (65.5%) were the most commonly reported global health experience available to trainees. In addition, the majority of trainees reported they were either “very likely” (27.0%) or “moderately likely” (34.8%) to apply for an elective global health curriculum, with the most interest noted in an elective rotation abroad (82.8%). Trainees (72.1%) and PDs (89.5%) both identified the cost of international electives to be the primary barriers to participation in global health education. Our results indicated that the development of a rehabilitation global health curriculum available for PM&R trainees throughout the United States may provide an opportunity for trainee development, foster a positive relationship with international partners, and improve the availability of rehabilitation resources for the aging population.
Ultrasound-Guided Injections for Treatment of Facial Paralysis Sequelae: A Randomized Study on Body Donors
Authors: Vejbrink Kildal Villiam , Rodriguez-Lorenzo Andrés , Pruidze Paata , Reissig Lukas , Weninger Wolfgang J. , Tzou Chieh-Han John , Jonsson Lars , Meng Stefan
Published: June 2023

Background:

Botulinum toxin injection is the gold standard treatment of synkinesis and gustatory hyperlacrimation in facial paralysis patients. However, poor injection accuracy may lead to suboptimal treatment results and complications. Diplopia, ptosis, and lagophthalmos are common after lacrimal gland injections. Intra-ocular injections have been reported in the treatment of both synkinesis and excessive tearing. Ultrasound guidance should increase injection accuracy in the facial region, but this has not been proven.

Methods:

Twenty-six hemifaces of non-embalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated through several measures.

Results:

Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance (p<0.001). This was most pronounced in the lacrimal gland (62% vs. 8%), depressor anguli oris (100% vs. 46%), and mentalis (100% vs. 54%) (p<0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance vs. 29% without (p<0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance vs. 83% without (p<0.01). Twenty-three percent of landmark-guided depressor anguli oris injections stained the facial artery (p=0.22).

Conclusions:

Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in surrounding tissue when compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in facial paralysis patients.
Sleep-disordered Breathing in Children With Craniofacial Anomalies
Authors: Pongchangyoo Juthamas , Hantragool Sumalee , Rojvachiranonda Nond , Niyomkarn Watit
Published: June 2023

Sleep-disordered breathing (SDB) is a common disorder in children, characterized by snoring and/or increased breathing force due to narrowing and increased upper airway collapse while sleeping. Over the last decade, it has been recognized that SDB occurs more frequently in children with craniofacial anomalies, but data in Thailand is quite limited. This study retrospective descriptive study aims to find the prevalence of SDB among children with craniofacial anomalies in Thailand and associated risk factors by collecting data among Thai children with congenital craniofacial anomalies younger than 15 years old who visited the Princess Sirindhorn Craniofacial Center at King Chulalongkorn Memorial Hospital between 2016 and 2021. All children were defined into syndromic and nonsyndromic groups. Data collected from the electronic medical record includes baseline characteristics, diagnosis of craniofacial anomalies, associated risk factors, diagnosis of SDB, diagnostic tools, and treatment. Total of 512 children, there were 80 children (15.4%) who had SDB. The most diagnosis was 51 (10%) obstructive sleep apnea followed by 27 (5.3%) primary snoring and 2 (0.4%) obstructive hypoventilation. The prevalence of SDB in the syndromic group was 43 (46.7%) while the nonsyndromic group was 37 (8.6%), (P<0.001). The risk factors associated with SDB were overweight, allergic rhinitis, tonsillar hypertrophy, high arch palate, micrognathia, and syndromic craniofacial anomalies. The prevalence of SDB is higher in children with syndromic craniofacial anomalies than in the nonsyndromic group. Knowledge of the prevalence and related factors can lead to better care, including early screening and monitoring of SDB in craniofacial patients.
Avoidance-motivational intensity modulated the effect of negative emotion on working memory
Authors: Hou Tianya , Xie Yawei , Zhang Jianguo , Sun Zhuoer , Yin Qianlan , Li Ziqiang , Cai Wenpeng , Dong Wei , Deng Guanghui , Mao Xiaofei
Published: June 2023

Although many studies have explored the association between negative emotion and working memory, the findings remain controversial. The present study investigated the role of avoidance-motivational intensity in modulating the effect of negative emotion on different processes (maintenance versus manipulation) of verbal and spatial working memory. Two experiments employed the modified delayed match-to-sample paradigms to separate the two processes of verbal and spatial working memory under different emotional states, respectively. In Experiment 1, participants were asked to perform the delayed match-to-sample task with or without reordering the characters (manipulation process of verbal working memory). In Experiment 2, mental rotation was used as the manipulation process of spatial working memory. The results showed that negative emotion only affected the manipulation process, but not the maintenance process. Relative to neutral and low avoidance-motivated negative conditions, the manipulation processes of both types of working memory were impaired under the high avoidance-motivated negative condition. No significant difference was observed between low avoidance-motivated negative condition and neutral condition. Our results are discussed in relation to efficiency processing theory and motivational dimensional model of affect. We conclude that negative emotional states with high avoidance-motivational intensity impair the manipulation process of verbal and spatial working memory.
Cold and ultracold molecules in the twenties
Authors: Softley Timothy P.
Published: June 2023

A diversity of experimental techniques has been developed over the last 25 years to create samples of molecular gases at temperatures close to the Absolute Zero—here we consider samples in the range from 10s of Kelvin (cold) down to 10s of nanoKelvin (ultracold). In these exotic physical environments, a range of novel experiments can be conducted which bring high levels of control over the properties of these ‘almost stationary’ molecules, in some cases with control over single trapped molecules achievable. In this article, recent advances in this field since 2020, both in terms of the ability to produce and manipulate the molecules and understand their properties, and also in the development of new applications of these technologies, are highlighted. Applications include observing explicit ‘quantum effects’ in chemical reactivity, developing an understanding of chemistry in cold astrophysical media, the creation of exotic phases of matter, the use of trapped molecules in quantum computation and simulations systems, and the use of very high-precision spectroscopic measurements to answer fundamental physics questions beyond the standard model of particle physics.
Recent origin and diversification accompanied by repeated host shifts of thallus-mining flies (Diptera: Agromyzidae) on liverworts and hornworts
Authors: Kato Makoto , Yamamori Luna , Imada Yume , Sota Teiji
Published: June 2023

Despite the vast diversity of phytophagous insects that feed on vascular plants (tracheophytes), insects that feed on bryophytes remain understudied. Agromyzidae, one of the most species-rich phytophagous clades in Diptera, consists mainly of leaf-mining species that feed on tracheophytes. However, a recent discovery of thallus-mining species on liverworts and hornworts within the
Liriomyza
group of Phytomyzinae provides an opportunity to study host shifts between tracheophytes and bryophytes. This study aimed to explore the origin and diversification of thallus-miners and estimate the pattern and timing of host shifts. Phylogenetic analysis of Phytomyzinae has revealed that the thallus-mining agromyzids formed a separate clade, which was sister to a fern pinnule-miner. The diversification of bryophyte-associated agromyzids since the Oligocene involved multiple host shifts across various bryophyte taxa. The diversification of the thallus-mining
Phytoliriomyza
may have occurred at the same time as the leaf-mining agromyzid flies on herbaceous plants, indicating a dynamic history of interactions between bryophytes and herbivores in angiosperms-dominated ecosystems.
The evolution of masturbation is associated with postcopulatory selection and pathogen avoidance in primates
Authors: Brindle Matilda , Ferguson-Gow Henry , Williamson Joseph , Thomsen Ruth , Sommer Volker
Published: June 2023

Masturbation occurs throughout the animal kingdom. At first glance, however, the fitness benefits of this self-directed behaviour are unclear. Regardless, several drivers have been proposed. Non-functional hypotheses posit that masturbation is either a pathology, or a byproduct of high underlying sexual arousal, whereas functional hypotheses argue an adaptive benefit. The Postcopulatory Selection Hypothesis states that masturbation aids the chances of fertilization, while the Pathogen Avoidance Hypothesis states that masturbation helps reduce host infection by flushing pathogens from the genital tract. Here, we present comprehensive new data documenting masturbation across the primate order and use these, in conjunction with phylogenetic comparative methods, to reconstruct the evolutionary pathways and correlates of masturbation. We find that masturbation is an ancient trait within the primate order, becoming a more common aspect of the haplorrhine behavioural repertoire after the split from tarsiers. Our analyses provide support for both the Postcopulatory Selection and Pathogen Avoidance Hypotheses in male primates, suggesting that masturbation may be an adaptive trait, functioning at a macroevolutionary scale.
Invertebrate biodiversity continues to decline in cropland
Authors: Mancini Francesca , Cooke Rob , Woodcock Ben A. , Greenop Arran , Johnson Andrew C. , Isaac Nick J. B.
Published: June 2023

Modern agriculture has drastically changed global landscapes and introduced pressures on wildlife populations. Policy and management of agricultural systems has changed over the last 30 years, a period characterized not only by intensive agricultural practices but also by an increasing push towards sustainability. It is crucial that we understand the long-term consequences of agriculture on beneficial invertebrates and assess if policy and management approaches recently introduced are supporting their recovery. In this study, we use large citizen science datasets to derive trends in invertebrate occupancy in Great Britain between 1990 and 2019. We compare these trends between regions of no- (0%), low- (greater than 0–50%) and high-cropland (greater than 50%) cover, which includes arable and horticultural crops. Although we detect general declines, invertebrate groups are declining most strongly in high-cropland cover regions. This suggests that even in the light of improved policy and management over the last 30 years, the way we are managing cropland is failing to conserve and restore invertebrate communities. New policy-based drivers and incentives are required to support the resilience and sustainability of agricultural ecosystems. Post-Brexit changes in UK agricultural policy and reforms under the Environment Act offer opportunities to improve agricultural landscapes for the benefit of biodiversity and society.
Capture Efficiency Of Long-Adapter Single-Strand Oligonucleotide Probe Libraries
Authors: Chkaiban Lamia , Tosi Lorenzo , Parekkadan Biju
Published: June 2023

High throughput techniques that can massively produce in parallel, longer DNA sequences of interest can accelerate the decoding of gene functions. LASSO probes are a molecular biology tool that can enrich for DNA targets in a genomic sample via a multiplexed, single-pot reaction for downstream sequencing and/or cloning. Here we have explored aspects of process development and the design of the probes that relate to binding thermodynamics to determine impact on cloned library sequences. Control of ligase concentration, polymerase type, and melting temperature of probe are critical when translating the use of LASSO probes for homogeneous and high fidelity DNA capture.
Micro-circulating hyperdynamic blood flow as a key pathogenic factor in early sepsis
Authors: Feng X.H. , Liu Wei , Sun Y.B. , Zeng Y. , Yu Bu-Wei
Published: June 2023

Objective

The pathogenesis of sepsis is still unknown. Sepsis 3.0 points out that “how to define sepsis and septic shock itself is still a challenge”. This study confirmed the inevitability and universality of Hyperdynamic microcirculation in sepsis, and put forward the detoxification mechanism of Hyperdynamic blood flow and the “Feng-Bernoulli warm shock” mechanism, that is, the pathogenic mechanism of sepsis.

Methods

Sepsis models of pigs, rabbits and sheep were established by intravenous injection of lipopolysaccharide (LPS) and cecal ligation and perforation (CLP), and the changes of sublingual microcirculation velocity in the same branch before and after modeling were detected. SD rat model of mild sepsis was established to verify that the acceleration of blood flow is the manifestation of immune detoxification mechanism.

Results

The blood flow in the same branch was accelerated after the animal sepsis model was established, which was more than doubled on average. The microcirculation blood flow accelerated before the change of cardiac output CO. Rats entered a toxic state after the rapid blood flow occurred, but they could heal themselves.

Conclusion

The acceleration of microcirculation blood flow in sepsis is inevitable and universal, which is the cause of high output and low resistance of sepsis, and has the functions of accelerating detoxification and immunity. However, due to Bernoulli effect, it will cause oxygen exchange disorder, which is named “Feng-Bernoulli warm shock”, ultimately leading to hypoxia. This is the primary pathogenic mechanism of early sepsis.
Body Weight and Cardio-respiratory Fitness: Predictors of Physical Function Capacity among Older Adults
Authors: Aloko Eric Ayine , Seibu Munkaila , Apaak Daniel , Sarpong Emmanuel O. , Sorkpor Stephen R. , Ansah Edward W.
Published: June 2023

Ageing is an inevitable part of human life, thus, everyone may grow and become old. The ageing process is characterized by reduced physical activity, accumulation of fat and loss of muscle mass resulting in weight gain and reduced cardio-respiratory function that leads to loss of physical function capacity . Therefore, t he purpose of this study was to determine the extent to which body weight and cardio-respiratory endurance predict physical functional capacity of older adults in Navrongo, Ghana. This study employed quantitative cross-sectional design, using a multistage sampling method with 998 aged (60yrs+) participants. The senior fitness test battery, international physical activity questionnaire (IPAQ) short form for elderly, weighing scale and tape measure were used to collect the data. The independent t-test and multiple regression were applied to analyse the data. The results indicated that physical activity levels were generally minimal among both men and women, but women were more overweight, had reduced cardio-respiratory function and physical function capacity. It is concluded that, body mass index and cardio-respiratory endurance are significant predictors of physical function capacity among older adults in Navrongo. It is recommended that, education on the health benefits is provided and regular participation in physical activity is done to promote regular exercise among these older adults. A longitudinal study is needed to explore the moderation-mediation role of physical activity on the relation of cardio-respiratory function and physical function capacity among older adults.
Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus
Authors: Brézellec Pierre
Published: June 2023

Abstract

Since the publication of the genome of SARS-CoV-2 – the causative agent of COVID-19 – in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although effcient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in “divergent organisms”. In order to improve the annotation of SARS-CoV-2 proteins, we used the HHpred protein annotation tool. To avoid “false positive predictions” as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs), such as Lutropin-choriogonadotropic hormone receptor, primarily belonging to the “Rhodopsin family”. To further investigate these similarities, we compared Prominin 1 and Lutropin-choriogonadotropic hormone receptor to a set of viral proteins using HHPRED. Interestingly, Prominin 1 showed similarities with 6 viral Spike glycoproteins, primarily from coronaviruses. Equally interestingly, Lutropin-choriogonadotropic hormone receptor showed similarities with 23 viral G-protein coupled receptors, particularly from Herpesvirales. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
Defining Microbial Community Functions in Chronic Human Infection with Metatranscriptomics
Authors: Adekoya Aanuoluwa E. , Kargbo Hoody A. , Ibberson Carolyn B.
Published: June 2023

Chronic polymicrobial infections (cPMIs) harbor complex bacterial communities with diverse metabolic capacities, leading to competitive and cooperative interactions. Although the microbes present in cPMIs have been established through culture-dependent and -independent methods, the key functions that drive different cPMIs and the metabolic activities of these complex communities remain unknown. To address this knowledge gap, we analyzed 102 published metatranscriptomes collected from cystic fibrosis sputum (CF) and chronic wound infections (CW) to identify key bacterial members and functions in cPMIs. Community composition analysis identified a high prevalence of pathogens, particularlyStaphylococcusandPseudomonas, and anaerobic members of the microbiota, includingPorphyromonas, Anaerococcus, and Prevotella. Functional profiling with HUMANn3 and SAMSA2 revealed that while functions involved in bacterial competition, oxidative stress response, and virulence were conserved across both chronic infection types, ≥40% of the functions were differentially expressed (padj < 0.05, fold-change >2). Higher expression of antibiotic resistance and biofilm functions were observed in CF, while tissue destructive enzymes and oxidative stress response functions were highly expressed in CW samples. Of note, strict anaerobes had negative correlations with traditional pathogens in both CW (P= -0.43) and CF (P= -0.27) samples and they significantly contributed to the expression of these functions. Additionally, we show microbial communities have unique expression patterns and distinct organisms fulfill the expression of key functions in each site, indicating the infection environment strongly influences bacterial physiology and that community structure influences function. Collectively, our findings indicate that community composition and function should guide treatment strategies for cPMIs.

Importance

The microbial diversity in polymicrobial infections (PMIs) allows for community members to establish interactions with one another which can result in enhanced disease outcomes such as increased antibiotic tolerance and chronicity. Chronic PMIs result in large burdens on health systems, as they affect a significant proportion of the population and are expensive and difficult to treat. However, investigations into physiology of microbial communities in actual human infection sites is lacking. Here, we highlight that the predominant functions in chronic PMIs differ, and anaerobes, often described as contaminants, may be significant in the progression of chronic infections. Determining the community structure and functions in PMIs is a critical step towards understanding the molecular mechanisms that drive microbe-microbe interactions in these environments.
Structural Basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkB
Authors: Kot Erik F. , Goncharuk Sergey A. , Franco María Luisa , Arseniev Alexander S. , Benito-Martínez Andrea , Costa Mario , Cattaneo Antonino , Vilar Marçal , Mineev Konstantin S.
Published: June 2023

Neurotrophin receptors of the Trk family are involved in the regulation of brain development and neuroplasticity, and therefore can serve as targets for anti-cancer and stroke-recovery drugs, antidepressants, and many others. The structures of Trk protein domains in various states upon activation need to be elucidated to allow rational drug design. However, little is known about the conformations of the transmembrane and juxtamembrane domains of Trk receptors. In the present study, we employed NMR spectroscopy to solve the structure of the TrkB dimeric transmembrane domain in the lipid environment. We verified the structure using mutagenesis and confirmed that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provided a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.
Structural Organization of the Retriever-CCC Endosomal Recycling Complex
Authors: Boesch Daniel J. , Singla Amika , Han Yan , Kramer Daniel A. , Liu Qi , Suzuki Kohei , Juneja Puneet , Zhao Xuefeng , Long Xin , Medlyn Michael J. , Billadeau Daniel D. , Chen Zhe , Chen Baoyu , Burstein Ezra
Published: June 2023

The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of VPS35L, VPS26C and VPS29, together with the CCC complex comprising CCDC22, CCDC93, and COMMD proteins, plays a crucial role in this process. The precise mechanisms underlying Retriever assembly and its interaction with CCC have remained elusive. Here, we present the first high-resolution structure of Retriever determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog, Retromer. By combining AlphaFold predictions and biochemical, cellular, and proteomic analyses, we further elucidate the structural organization of the entire Retriever-CCC complex and uncover how cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with Retriever-CCC-mediated endosomal recycling.
Automatic multisensory integration follows subjective confidence rather than objective performance
Authors: Gao Yi , Xue Kai , Odegaard Brian , Rahnev Dobromir
Published: June 2023

It is well known that sensory information from one modality can automatically affect judgments from a different sensory modality. However, it remains unclear what determines the strength of the influence of an irrelevant sensory cue from one modality on a perceptual judgment for a different modality. Here we test whether the strength of multisensory impact by an irrelevant sensory cue depends on participants’ objective accuracy or subjective confidence for that cue. We created visual motion stimuli with low vs. high overall motion energy, where high-energy stimuli yielded higher confidence but lower accuracy in a visual-only task. We then tested the impact of the low- and high-energy visual stimuli on auditory motion perception. We found that the high-energy visual stimuli influenced the auditory motion judgments more strongly than the low-energy visual stimuli, consistent with their higher confidence but contrary to their lower accuracy. A computational model assuming common principles underlying confidence reports and multisensory integration captured these effects. Our findings show that automatic multisensory integration follows subjective confidence rather than objective performance and suggest the existence of common computations across vastly different stages of perceptual decision making.