bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraocular Suture Technique for Flapless Two-Point Fixation of Four Fenestrated Haptics Intraocular Lenses
Authors: Zhang Yingxu , Zheng Jinbiao , Liu Jiahui
Published: January 2022

Purpose:

To describe a flapless technique for two-point fixation of intraocular lens (IOL) with four fenestrated haptics.

Methods:

A transconjunctival puncture of 1-mL syringe needle was used to guide the suture needle out of the eye. The suture was taken out of the eye through the corneal incision, passed through the pair of fenestrated haptics of the IOL and then securely tied with overhand knots. The folded IOL was implanted into the posterior chamber. The anchor knots were created by both ends of the thread approximately 4 mm to 5 mm apart from the transconjunctival puncture and was intrasclerally buried.

Results:

The technique was used in 18 eyes (18 patients). The mean postoperative follow-up period was 17.22 ± 8.82 months. The IOLs of all the eyes remained well positioned and stable at the final follow-up. The visual acuities of all the eyes were improved postoperatively. No suture loosening, suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed in any of the patients.

Conclusion:

The present technique provides minimal trauma and reliable stability for the two-point transscleral fixation of four fenestrated haptics IOL.
Strategies Employed by Forensic Community Mental Health Nurses to Resolve Difficulties in Supporting Offenders With Mental Disorders Under the Medical Treatment and Supervision Act in Japan
Authors: Okuda Jun , Endo Yoshimi
Published: January 2022

Objective

This study aimed to identify the strategies used by forensic community mental health nurses to resolve difficulties in supporting offenders with mental disorders under the Medical Treatment and Supervision Act in Japan.

Method

Interviews were conducted with 13 nurses, and the data were analyzed using content analysis.

Results

The study identified the strategies for difficulties in (a) assessing and managing risk potential of forensic service patients, (b) addressing offending behavior, (c) managing the transition of patients, (d) supporting patients to understand the impact of justice processes and applying knowledge of legislation to nursing, and (e) promoting the role of forensic community mental health nurses within the multidisciplinary team.

Conclusions

The findings can benefit and support forensic community mental health nurses' practices. The Japanese forensic community mental health nurses experiencing difficulties and providing home visits to patients can utilize the identified strategies.
Early vascular healing after implantation of the polymer-free biolimus-eluting stent or the ultrathin strut biodegradable polymer sirolimus-eluting stent in patients with ST-segment elevation myocardial infarction
Authors: Hansen Kirstine N. , Maeng Michael , Antonsen Lisbeth , Maehara Akiko , Jakobsen Lars , Ellert Julia , Terkelsen Christian J. , Ahlehoff Ole , Thim Troels , Fallesen Christian O. , Noori Manijeh , Veien Karsten T. , Jensen Lisette O. , Christiansen Evald H.
Published: January 2022

Objective

To evaluate the difference in early vascular healing between the ultrathin-strut biodegradable-polymer sirolimus-eluting Orsiro stent (O-SES) and the polymer-free biolimus-A9-eluting BioFreedom stent (BF-BES), assessed with optical coherence tomography (OCT) after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarctions (STEMIs).

Methods

Eighty patients with STEMI who underwent primary PCI were randomly allocated 1:1 to treatment with BF-BES or O-SES. OCT was acquired after PCI and at 1-month follow-up. The primary endpoint was 1-month OCT-assessed vascular healing index based on the presence of uncovered and malapposed stent struts and intraluminal filling defects where low vascular healing index indicated favorable vascular healing.

Results

At 1-month, the vascular healing index was similar in O-SES 11.5 [interquartile range (IQR) 9.5–17.5], compared to BF-BES 11.5 (IQR 7.1–12.5; P = 0.14). Percentage of uncovered struts [O-SES 31.5% (IQR 20.7–41.9), P = 0.43] vs. BF-BES 27.8% (IQR 19.4–41.9; P = 0.44), and median volume of neointimal hyperplasia [O-SES 4.9 mm3 (IQR 1.4–13.1) vs. BF-BES 7.1 mm3 (IQR 2.8–17.0), P = 0.18] did not differ significantly between the two stent groups. Complete coverage was not observed in any of the stents. The percentages of stents with malapposition did not differ significantly (O-SES 87.1% vs. BF-BES 71.4%, P = 0.14) whereas percentage of malapposed struts [O-SES 3.5% (IQR 0.8–5.5) vs. BF-BES 0.8% (IQR 0.0–1.8), P = 0.003] was lower in the BF-BES group.

Conclusion

In patients with STEMI, the drug-coated BF-BES and the thin strut O-SES had similar vascular healing index at 1-month. However, the thin O-SES struts were more often malapposed.
Gamma-knife radiosurgery for headache relief in a patient with pituitary metastasis
Authors: Peker Halil Olgun , Seker Askin
Published: January 2022

Rationale:

Pituitary metastasis is infrequent and has no pathognomonic symptoms. Surgical exploration is usually needed to establish the diagnosis and implement the appropriate therapy. Given that most affected patients are diagnosed in end-stage primary disease, the main aim of treatment for pituitary metastasis is to relieve symptoms. We report a case of pituitary metastasis in which gamma-knife radiosurgery (GRS) relieved headache pain that persisted after surgery for pituitary metastasis.

Patient concerns:

A 76-year-old man presented with severe headache.

Diagnosis:

Cranial magnetic resonance imaging demonstrated a pituitary mass invading the internal carotid artery and cavernous sinus.

Interventions:

All medical therapy for headache treatment failed. The patient underwent surgical resection via endoscopic endonasal transsphenoidal surgery but the tumor could only be partially resected because it adhered to vital structures. Postoperatively, headache persisted despite all attempted medical treatments. We performed GRS with the aim of resolving the severe headache.

Outcomes:

Ten days after GRS, the patient's headache had completely resolved.

Lesson:

Surgical decompression may not resolve headache in patients with pituitary metastasis. In such cases, it is important to recognize that GRS may provide rapid relief or resolution, as well as better quality of life, even though survival time may be limited.
Midshaft clavicle fracture with hypertrophy of the fractured end
Authors: Lin Shaobai , Mei Runhong , Jiang Lang , Zhong Duming , Zhang Guangquan , Yu Xuefeng
Published: January 2022

Introduction:

Midshaft clavicle fractures are common fractures, but clavicle fractures with hypertrophy of the fractured end are rare. To the best of our knowledge, there are no reports describing this peculiar form of fracture.

Patient concerns:

A 68-year-old woman was admitted to the orthopedic department for treatment of left shoulder joint swelling and pain with limited mobility for 1 day duration She had a history of falls and an old left distal radius fracture, but no history of left shoulder joint swelling, pain, and limited mobility.

Diagnosis:

1. Midshaft fracture of the left clavicle 2. Motor neuron injury 3. Multilevel cervical intervertebral disc herniation. 4. Brain atrophy 5. Old left distal radius fracture.

Interventions:

Surgical treatment was performed after detailed preoperative evaluation. During surgery, the clavicle fracture was anatomically reduced under direct vision (unusually, the fracture end was displaced during intraoperative fluoroscopy). After fracture reduction, one eight-hole locking plate was fixed with three locking screws at each end of the fracture. After the surgery, the patient was instructed to perform rehabilitation training.

Outcomes:

The sutures were removed on the 12th postoperative day, and the incision wound healing was good. Follow-up at one month after surgery revealed no swelling or pain at the left clavicle fracture site and both active and passive ranges of motion of the left shoulder joint were good.

Conclusion:

For clavicle fractures with hypertrophy of the fractured ends in the elderly, after excluding pathological fractures caused by tumors, satisfactory results can be obtained as long as strong internal fixation is achieved. In the midshaft clavicle fracture with hypertrophy of the fractured end, whether to achieve the reduction criteria under direct vision or intraoperative fluoroscopy imaging should be determined on the basis of the patient's actual condition. Motor neuron injury may promote the healing of clavicle fractures due to restricted motor function that promotes fracture healing.
Metabolic associated fatty liver disease and acute-on-chronic liver failure: common themes for common problems
Authors: Córdova-Gallardo Jacqueline , Keaveny Andrew P. , Qi Xingshun , Méndez-Sánchez Nahum
Published: January 2022

Metabolic associated fatty liver disease (MAFLD) affects 20–30% of the worldwide population and is becoming the most common cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). MAFLD is the hepatic expression of metabolic dysfunction correlated with a variety of metabolic comorbidities including obesity, dyslipidemia, hypertension and type 2 diabetes (T2DM). Obesity, altered gut permeability, chronic inflammation and dysbiosis related to MAFLD might predispose patients with cirrhosis to the development of acute-on-chronic liver failure (ACLF); however, this relationship remains unclear. ACLF is a syndrome with high short-term mortality, presenting with acute hepatic decompensation associated with organ failures in patients with underlying chronic liver disease with or without an identifiable precipitating event. While this syndrome can occur in any patient with cirrhosis, the increasing prevalence of cirrhosis due to MAFLD is of great concern because, in a recent analysis, MAFLD was the fastest rising cause of cirrhosis associated with ACLF among patients listed for LT in the US. In this review, we will discuss the current knowledge on MAFLD and the development of ACLF.
Long‐Term Follow‐up and Predictors of Complicated Disease Behavior in Pediatric Crohn's Disease Patients
Authors: Kori Michal , Avidan Maya , Topf‐Olivestone Chani
Published: January 2022

Objective:

Identifying predictors of inflammatory bowel disease (IBD) outcome in order to optimize individual patient management in has become an important goal. We aimed to describe the long‐term outcome of pediatric Crohn disease (CD) patients and identify risk factors for complicated behavior.

Methods:

Pediatric CD patients diagnosed between 1998 and 2014, with long‐term follow‐up were included. Baseline data; age, gender, weight/height/BMI percentiles, and family history of IBD. Disease characteristics (Paris classification), laboratory testing, imaging and treatment were documented. Outcome data; evidence of stricturing or penetrating disease, hospitalizations, surgical intervention, malignancies, and mortality.

Results:

Of 93 patients included, mean age at diagnosis 13.5 (±3.2), 51 (55%) male, median follow‐up 10.3 years (±4 SD(. Disease location at diagnosis: 29 (31.2%) distal ileum, 17 (18.3%) colonic, 40 (43.0%) ileo‐colonic. Seven (7.5%) had upper gastrointestinal and 36 (38.7%) perianal involvement. Behavior at diagnosis, 68 (73.1%) inflammatory (B1), and 25 (26.9%) complicated [(B2 (stricturing) and/or B3 (penetrating)]. Twenty (23.2%) of B1 evolved to B2 and/or B3, thus by the end of follow‐up 45 (48.4%) had complicated behavior. Sixty‐seven (72%) were hospitalized, 20 (21.5%) underwent surgery, two developed malignancy with no mortalities. In a logistic regression model, growth delay (hazard ratio [HR], 5.02 [1.10–22.85], P = 0.037) and low albumin levels (HR, 3.97 [1.32–11.97], P = 0.014) at diagnosis were predictors of complicated disease in adulthood.

Conclusions:

Over a quarter of pediatric Crohn disease patients present with complicated behavior. During follow‐up another quarter progress to complicated disease behavior. Delayed growth and low albumin at diagnosis predict progression.
Malnutrition Among Hospitalized Adult Patients
Authors: Chughtai Amina , Tanweer Afifa , Abid Arooj
Published: January 2022

Hospital malnutrition, although well established, has remained underrecognized in health care settings. This study aimed at determining the prevalence and factors associated with hospital malnutrition in Lahore, Pakistan. A sample of 937 hospitalized patients was screened for malnutrition using a Subjective Global Assessment (SGA). More than half (59.4%) of the sample was found to be undernourished, of which 26.4% was severely malnourished (SGA-C). Age more than 60 years (odds ratio [OR] = 0.574, P < .05), comorbidities (OR = 1.388, P = .014), and specific disease conditions (cancer and renal diseases) (OR = 3.291; OR = 3.042, P < .05, respectively) increased the risk of undernourishment (SGA-B&C). High prevalence of disease-associated malnutrition among hospitalized patients urgently calls for preadmission screening.
Frequent Quantitation of Circulating Tumor Cells Predictive of Real-Time Therapy Response
Authors: Lim Christine M. , Shi Junli , Vo Jess , Phyo Wai Min , Hu Min , Tan Min Chin , Tee Augustine , Yap Yoon Sim , Nei Wenlong , Chan Daniel , Wong Seng Weng , Neo Meusia , Binte Mohammad Mazian Norhidayah , Ying Jackie Y. , Tan Min-Han , Liang Kaicheng , Mong Jamie
Published: January 2022

Precision medicine is playing an increasingly important role in cancer management and treatment. Specifically in the field of oncology, circulating tumor cells (CTCs) hold significant promise in enabling non-invasive prognostication and near real-time monitoring to individualize treatments. In this study, we present strong associations between CTC subtype counts with treatment response and tumor staging in lung, nasopharyngeal and breast cancers. Longitudinal analysis of CTC count changes over short-time windows further reveals the ability to predict treatment response close to real-time. Our findings demonstrate the suitability of CTCs as a definitive blood-based metric for continuous treatment monitoring. Robust processing of high-throughput image data, explainable classification of CTC subtypes and accurate quantification were achieved using an in-house image analysis system ‘CTC-Quant’, which showed excellent agreement with expert opinion upon extensive validation.
Does choice of athletic footwear affect musculoskeletal injury risk in US Coast Guard recruits? A retrospective cohort study
Authors: Fraser John J. , Pommier Ryan , MacGregor Andrew J , Silder Amy , Sander Todd C.
Published: January 2022

Context

Musculoskeletal injuries (MSKIs) are ubiquitous during initial entry military training, with overuse injuries in the lower extremities the most frequent. A common mechanism for overuse injuries is running, an activity that is an integral part of United States Coast Guard (USCG) training and a requirement for graduation.

Objective

Assess the effects of athletic footwear choice on lower quarter MSKI risk in USCG recruits.

Design

Descriptive Epidemiological Study

Setting

USCG Training Center, Cape May, NJ

Participants

A retrospective cohort study was performed in which 1229 recruits (1038 males, 191 females) were allowed to self-select athletic footwear during training. A group of 2876 recruits (2260 males, 616 females) who trained under a policy that required obligatory wear of prescribed athletic shoes served as a control.

Main Outcome Measures

Demographic data and physical performance were derived from administrative records. Injury data were abstracted from a medical tracking database. Multivariable logistic regression was used to assess group, age, sex, height, body mass, and run times on MSKI outcomes.

Results

Ankle-foot, leg, knee and lumbopelvic-hip complex diagnoses were ubiquitous in both groups (experimental: 20.37 to 29.34 per 1000 recruits; control: 18.08 to 25.59 per 1000 recruits). Group was not a significant factor for any of the injuries assessed. Sex was a significant factor in all injury types, with female recruits demonstrating ∼2.00 greater odds of experiencing running-related injuries (RRIs), overuse injuries, or any MSKI in general. When considering ankle-foot or bone stress injuries, the risk in female recruits was 3.73 to 4.11 greater odds than their male counterparts. Run time was a significant predictor in RRI, all overuse injuries, and for any MSKI in general.

Conclusion

While footwear choice did not influence MSKI risk in USCG recruits, female sex was a primary, nonmodifiable intrinsic risk factor.

Key Points

Self-selection of athletic footwear was not a significant factor for MSKI in USCG recruits, despite widespread reports of discomfort and perceived deleterious effects of wear.

MSKI continues to be a major source of morbidity in the recruit training population, with female sex found to be a robust and significant factor regardless of footwear choice.

While there is no indication that prescribed athletic footwear is associated with MSKI, policymakers should factor in individual preference when considering the mandate for wear.
Locations of burr holes are associated with recurrence after single burr hole drainage surgery for chronic subdural hematoma
Authors: Hashimoto Hiroaki , Maruo Tomoyuki , Kimoto Yuki , Nakamura Masami , Fujinaga Takahiro , Ushio Yukitaka
Published: January 2022

Objective

This study aimed to reveal the relation between chronic subdural hematomas (CSDH) recurrence and locations of CSDH and burr holes.

Methods

Initial single burr hole surgeries for CSDH with a drainage tube between April 2005 and October 2021 at Otemae Hospital were enrolled. Patients’ medical records, CSDH volume, and CSDH computed tomography values (CTV) were evaluated. The locations of CSDH and burr holes were assessed using Montreal Neurological Institute coordinates.

Results

We enrolled 223 patients (bilateral CSDH in 34 patients), and 257 surgeries were investigated. Rate of CSDH recurrence requiring reoperation (RrR) was 13.5%. RrR rate was significantly higher in patients aged ≥76 years, bilateral CSDH, and postoperative hemiplegia. In RrR, preoperative CSDH volume was significantly larger, and CTV was significantly smaller. Locations of CSDH had no influence on recurrence. However, in RrR, locations of burr holes were more lateral and more ventral. Multivariate Cox proportional hazards regression analysis showed that bilateral CSDH, more ventral burr hole positions, and postoperative hemiplegia were risk factors for recurrence.

Conclusions

Locations of burr holes related to recurrence. In RrR, CSDH profiles had larger volume and less CTV. Hemiplegia after burr hole surgery is a warning sign for RrR.
Virtually the same? Evaluating the effectiveness of remote undergraduate research experiences
Authors: Hess Riley A. , Erickson Olivia A. , Cole Rebecca B. , Isaacs Jared M. , Alvarez-Clare Silvia , Arnold Jonathan , Augustus-Wallace Allison , Ayoob Joseph C. , Berkowitz Alan , Branchaw Janet , Burgio Kevin R. , Cannon Charles H. , Ceballos Ruben Michael , Cohen C. Sarah , Coller Hilary , Disney Jane , Doze Van A. , Eggers Margaret J. , Ferguson Edwin L. , Gray Jeffrey J. , Greenberg Jean T. , Hoffmann Alexander , Jensen-Ryan Danielle , Kao Robert M. , Keene Alex C. , Kowalko Johanna E. , Lopez Steven A. , Mathis Camille , Minkara Mona , Murren Courtney J. , Ondrechen Mary Jo , Ordoñez Patricia , Osano Anne , Padilla-Crespo Elizabeth , Palchoudhury Soubantika , Qin Hong , Ramírez-Lugo Juan , Reithel Jennifer , Shaw Colin A. , Smith Amber , Smith Rosemary J. , Tsien Fern , Dolan Erin L.
Published: January 2022

In-person undergraduate research experiences (UREs) promote students’ integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration. To address this, we investigated indicators of scientific integration for students who participated in remote life science URE programs in summer 2020. We found that these students experienced gains in their scientific self-efficacy and scientific identity similar to results reported for in-person UREs. We also found that these students perceived high benefits and low costs of doing research at the outset of their programs, and their perceptions did not change despite the remote circumstances. Yet, their perceptions differed by program, indicating that programs differentially affected students’ perceptions of the costs of doing research. Finally, we observed that students with prior research experience made greater gains in self-efficacy and identity, as well as in their perceptions of the alignment of their values with those of the scientific community, in comparison to students with no prior research experience. This finding suggests that additional programming may be needed for undergraduates with no prior experience to benefit from remote research.
Structural basis of Omicron neutralization by affinity-matured public antibodies
Authors: Sheward Daniel J. , Pushparaj Pradeepa , Das Hrishikesh , Kim Changil , Kim Sungyong , Hanke Leo , Dyrdak Robert , McInerney Gerald , Albert Jan , Murrell Ben , Karlsson Hedestam Gunilla B. , Hällberg B. Martin
Published: January 2022

The SARS-CoV-2 Omicron1 Variant of Concern (B.1.1.529) has spread rapidly in many countries. With a spike that is highly diverged from that of the pandemic founder, it escapes most available monoclonal antibody therapeutics2,3 and erodes vaccine protection4. A public class of IGHV3-53-using SARS-CoV-2 neutralizing antibodies5,6 typically fails to neutralize variants carrying mutations in the receptor-binding motif7–11, including Omicron. As antibodies from this class are likely elicited in most people following SARS-CoV-2 infection or vaccination, their subsequent affinity maturation is of particular interest. Here, we isolated IGHV3-53-using antibodies from an individual seven months after infection and identified several antibodies capable of broad and potent SARS-CoV-2 neutralization, extending to Omicron without loss of potency. By introducing select somatic hypermutations into a germline-reverted form of one such antibody, CAB-A17, we demonstrate the potential for commonly elicited antibodies to develop broad cross-neutralization through affinity maturation. Further, we resolved the structure of CAB-A17 Fab in complex with Omicron spike at an overall resolution of 2.6 Å by cryo-electron microscopy and defined the structural basis for this breadth. Thus, public SARS-CoV-2 neutralizing antibodies can, without modified spike vaccines, mature to cross-neutralize exceptionally antigenically diverged SARS-CoV-2 variants.
Structure-function-dynamics relationships in the peculiar Planktothrix PCC7805 OCP1: impact of his-tagging and carotenoid type
Authors: Wilson Adjélé , Andreeva Elena A. , Nizinski Stanislaw J. , Talbot Léa , Hartmann Elisabeth , Schlichting Ilme , Burdzinski Gotard , Sliwa Michel , Kirilovsky Diana , Colletier Jacques-Philippe
Published: January 2022

The orange carotenoid protein (OCP) is a photoactive protein involved in cyanobacterial photoprotection. Here, we report on the functional, spectral and structural characteristics of the peculiar Planktothrix PCC7805 OCP (Plankto-OCP). We show that this OCP variant is characterized by higher photoactivation and recovery rates, and a stronger energy-quenching activity, compared to other OCP studied thus far. We characterize the effect of the functionalizing carotenoid and of his-tagging on these reactions, and identify the time scales on which these modifications affect photoactivation. The presence of a his-tag at the C-terminus has a large influence on photoactivation, thermal recovery and PBS-fluorescence quenching, and likewise for the nature of the carotenoid that additionally affects the yield and characteristics of excited states and the ns-s dynamics of photoactivated OCP. By solving the structures of Plankto-OCP in the ECN- and CAN-functionalized states, each in two closely-related crystal forms, we further unveil the molecular breathing motions that animate Plankto-OCP at the monomer and dimer levels. We finally discuss the structural changes that could explain the peculiar properties of Plankto-OCP.

Highlights

Complete functional characterization of Synechocystis and Planktothrix OCP

Hitherto unknown structures of ECN- and CAN-functionalized Planktothrix OCP

Insights into fs-s timescale photodynamics of ECN- and CAN-functionalized Synechocystis and Planktothrix OCP
Improving cassava bacterial blight resistance by editing the epigenome
Authors: Veley Kira M. , Elliott Kiona , Jensen Greg , Zhong Zhenhui , Feng Suhua , Yoder Marisa , Gilbert Kerrigan B. , Berry Jeffrey C. , Lin Zuh-Jyh Daniel , Ghoshal Basudev , Gallego-Bartolomé Javier , Norton Joanna , Motomura-Wages Sharon , Carrington James C. , Jacobsen Steven E. , Bart Rebecca S.
Published: January 2022

Pathogens rely on expression of host susceptibility (S) genes to promote infection and disease. As DNA methylation is an epigenetic modification that affects gene expression, blocking access to S genes through targeted methylation could increase disease resistance.Xanthomonas phaseolipv.manihotis, the causal agent of cassava bacterial blight (CBB), uses transcription activator-like20 (TAL20) to induce expression of the S geneMeSWEET10a. In this work, we direct methylation to the TAL20 effector binding element within theMeSWEET10apromoter using a synthetic zinc-finger DNA binding domain fused to a component of the RNA-directed DNA methylation pathway. We demonstrate that this methylation prevents TAL20 binding, blocks transcriptional activation ofMeSWEET10a in vivoand that these plants display decreased CBB symptoms while maintaining normal growth and development. This work therefore presents an epigenome editing approach useful for crop improvement.
Enhanced loss of retinoic acid network genes in Xenopus laevis achieves a tighter signal regulation
Authors: Abbou Tali , Bendelac-Kapon Liat , Sebag Audeliah , Fainsod Abraham
Published: January 2022

Retinoic acid (RA) is a major regulatory signal during embryogenesis produced from vitamin A (retinol) by an extensive, autoregulating metabolic and signaling network to prevent fluctuations that result in developmental malformations. Xenopus laevis is an allotetraploid hybrid frog species whose genome includes L (long) and S (short) chromosomes from the originating species. Evolutionarily, the X. laevis subgenomes have been losing either L or S homoeologs in about 43% of genes to generate singletons. In the RA network, out of the 47 genes, about 46% have lost one of the homoeologs, like the genome average. In contrast, RA metabolism genes from storage (retinyl esters) to retinaldehyde production exhibit enhanced gene loss with 75% singletons out of 28 genes. The effect of this gene loss on RA signaling autoregulation was studied. Employing transient RA manipulations, homoeolog gene pairs were identified in which one homeolog exhibits enhanced responses or looser regulation than the other, while in other pairs both homoeologs exhibit similar RA responses. CRISPR /Cas9 targeting of individual homoeologs to reduce their activity supports the hypothesis where the RA metabolic network gene loss results in tighter network regulation and more efficient RA robustness responses to overcome complex regulation conditions.
Heterogeneity of social cognition in temporo-parietal junction: Overlapping yet distinct representation between visual perspective-taking and theory of mind
Authors: Ogawa Kenji , Matsuyama Yuiko
Published: January 2022

Visual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in VPT and ToM. To clarify this point, the present study directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. VPT2-induced activations were compared with activations observed during a mental rotation task as a control task, whereas ToM-related activities were identified with a standard ToM localizer using false-belief stories. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. By comparing the activations induced by VPT2 and ToM in individual participants, we found that the peak voxels induced by ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activity areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have distinct representations, albeit partially overlapping, indicating the functional heterogeneity of social cognition within the TPJ.

Significance Statement

The temporo-parietal junction (TPJ) is consistently activated by social cognitive tasks such as visual perspective taking (VPT) and theory of mind (ToM) tasks. The present study investigated whether VPT and ToM have the same neural substrates within the TPJ using functional magnetic resonance imaging (fMRI) with a within-subjects design. While VPT and ToM tasks activated overlapping areas in the posterior part of the TPJ, the individual peak voxels induced by ToM were located significantly more anteriorly and dorsally compared with those observed during the VPT task. Moreover, they were spatially distinct from the nearby functional modules, such as the extrastriate body area, visual motion area, and posterior superior temporal sulcus. Our findings reveal the heterogeneity of social cognition representation within the TPJ.
Gene expression profiles of some prognostic markers in a human breast cell line (MCF7) exposed to Curcumin nanoparticles and nanocapsules
Authors: Shaker Emad S. , Nasr Ghada M. , Moawad Mahmoud
Published: January 2022

1.

Introduction

Worldwide, cancer is a significant public health problem. Curcumin exhibits anti-inflammatory, antiproliferative, and anticancer properties when used in medicine. Investigated study for Curcumin’s chemopreventive mechanism against human malignancies, this research examined the cellular and molecular alterations generated by curcumin modified compound in breast cancer (MCF-7) cell lines. Oncogenic EGFR and VEGFR2 mutations lead to the formation, invasion, and maintenance of malignant phenotypes in humans, including breast cancer. Studied prognostic markers such as C-myc and Ki67 in breast cancer, and the apoptotic gene as Caspase-3 have been done.

Aim of the work

The purpose of this study is to determine the therapeutic efficacy of curcumin nanoparticles and nanocapsules in breast cancer cell lines (MCF7).

Materials and methods

We used real-time PCR to assess the expression of the C-myc, Ki67, EGFR, VEGFR2, and Caspase-3 genes in MCF7 cells treated with Curcumin nanoparticles and nanocapsules.

Results

Curcumin nanoparticles and nanocapsules boosted apoptotic cell populations considerably regardless of the nanotechnology used. Additionally, the mRNA expression analysis results indicated that the mechanism activated by curcumin nanocapsules involved the upregulation of the oncogenes EGFR and VEGFR2. In comparison to curcumin nanoparticles, curcumin nanocapsules significantly reduced the expression of Ki67 and c-myc mRNAs in breast cancer cells. The mRNA expression study revealed that curcumin nanocapsules produce an increase in the apoptotic Caspase-3 gene production compared to cells treated with curcumin nanoparticles.

Conclusion

This work demonstrates that curcumin nanoparticles created using a novel mechanical process can be employed successfully as an anticancer agent. These findings add to our understanding of the molecular mechanisms behind curcumin nanocapsules’ anticancer activity in breast cancer.
Transglutaminase mediated asprosin oligomerization allows its tissue storage as fibers
Authors: Morcos Yousef A.T. , Pryymachuk Galyna , Lütke Steffen , Gerken Antje , Godwin Alan R. F. , Jowitt Thomas A. , Piekarek Nadin , Hoffmann Thorben , Niehoff Anja , Odenthal Margarete , Drebber Uta , Grisk Olaf , Ladilov Yury , Bloch Wilhelm , Callewaert Bert , Paulsson Mats , Hucklenbruch-Rother Eva , Baldock Clair , Sengle Gerhard
Published: January 2022

Asprosin, the C-terminal furin cleavage product of profibrillin-1, was reported to act as a hormone that circulates at nanomolar levels and is recruited to the liver where it induces G protein-coupled activation of the cAMP-PKA pathway and stimulates rapid glucose release into the circulation. Although derived upon C-terminal cleavage of fibrillin-1, a multidomain extracellular matrix glycoprotein with a ubiquitous distribution in connective tissues, little is known about the mechanisms controlling the bioavailability of asprosin in tissues. In the current view, asprosin is mainly produced by white adipose tissue from where it is released into the blood in monomeric form. Here, by employing newly generated specific asprosin antibodies we monitored the distribution pattern of asprosin in human and murine connective tissues such as placenta, and muscle. Thereby we detected the presence of asprosin positive extracellular fibers. Further, by screening established cell lines for asprosin synthesis we found that most cells derived from musculoskeletal tissues render asprosin into an oligomerized form. Our analyses show that asprosin already multimerizes intracellularly, but that stable multimerization via covalent bonds is facilitated by transglutaminase activity. Further, asprosin fiber formation requires an intact fibrillin-1 fiber network for proper linear deposition. Our data suggest a new extracellular storage mechanism of asprosin in an oligomerized form which may regulate its cellular bioavailability in tissues.
Proximity labeling reveals spatial regulation of the anaphase-promoting complex/cyclosome by a microtubule adaptor
Authors: Cao Xiaofu , Shah Adnan Shami , Sanford Ethan J. , Smolka Marcus B. , Baskin Jeremy M.
Published: January 2022

The anaphase-promoting complex/cyclosome (APC/C) coordinates advancement through mitosis via temporally controlled polyubiquitination of effector proteins. Despite the long-appreciated spatial organization of key events in mitosis mediated largely by cytoskeletal networks, the spatial regulation of APC/C, the major mitotic E3 ligase, is poorly understood. Here, we describe a microtubule-resident protein, PLEKHA5, as an interactor of APC/C and spatial regulator of its activity in mitosis. PLEKHA5 knockdown delayed mitotic progression, causing accumulation of APC/C substrates dependent upon the PLEKHA5–APC/C interaction. To assess the spatial importance of this interaction, we developed microtubule-localized proximity biotinylation tools, which revealed that depletion of PLEKHA5 decreased the extent of APC/C association with the microtubule cytoskeleton. This decreased APC/C microtubule-localization in turn prevented efficient loading of APC/C with its co-activator CDC20, leading to defects in E3 ligase catalytic activity. We propose that PLEKHA5 functions as an adaptor of APC/C that promotes its subcellular localization to microtubules and facilitates its activation by CDC20, thus ensuring the timely turnover of key mitotic APC/C substrates and proper progression through mitosis.
GWAS and functional studies implicate a role for altered DNA repair in the evolution of drug resistance in Mycobacterium tuberculosis
Authors: Naz Saba , Paritosh Kumar , Sanyal Priyadarshini , Khan Sidra , Singh Yogendra , Varshney Umesh , Nandicoori Vinay Kumar
Published: January 2022

The emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is alarming and demands in-depth knowledge for timely diagnosis. We performed genome-wide association analysis (GWAS) using 2237 clinical strains of Mtb to identify novel genetic factors that evoke drug resistance. In addition to the known direct targets, for the first time, we identified a strong association between the mutations in the DNA repair genes and the multidrug-resistant phenotype. To evaluate the impact of variants identified in the clinical samples in the evolution of drug resistance, we utilized knockouts and complemented strains in Mycobacterium smegmatis (Msm) and Mtb. Results show that variant mutations abrogated the function of MutY and UvrB. MutY variant showed enhanced survival compared with wild-type (Rv) when the Mtb strains were subjected to multiple rounds of ex vivo antibiotic stress. Notably, in an in vivo Guinea pig infection model, the MutY variant outcompeted the wild-type strain. Collectively, we show that novel variant mutations in the DNA repair genes abrogate their function and contribute to better survival under antibiotic/host stress conditions.
Multivalent interactions drive the Toxoplasma AC9:AC10:ERK7 complex to concentrate ERK7 in the apical cap
Authors: Back Peter S. , O’Shaughnessy William J. , Moon Andy S. , Dewangan Pravin S. , Reese Michael L. , Bradley Peter J.
Published: January 2022

The Toxoplasma inner membrane complex (IMC) is a specialized organelle that is crucial for the parasite to establish an intracellular lifestyle and ultimately cause disease. The IMC is composed of both membrane and cytoskeletal components, further delineated into the apical cap, body, and basal subcompartments. The apical cap cytoskeleton was recently demonstrated to govern the stability of the apical complex, which controls parasite motility, invasion, and egress. While this role was determined by individually assessing the apical cap proteins AC9, AC10, and the MAP kinase ERK7, how the three proteins collaborate to stabilize the apical complex is unknown. In this study, we use a combination of deletion analyses and yeast-2-hybrid experiments to establish that these proteins form an essential complex in the apical cap. We show that AC10 is a foundational component of the AC10:AC9:ERK7 complex and demonstrate that the interactions among them are critical to maintain the apical complex. Importantly, we identify multiple independent regions of pairwise interaction between each of the three proteins, suggesting that the AC9:AC10:ERK7 complex is organized by multivalent interactions. Together, these data support a model in which multiple interacting domains enable the oligomerization of the AC9:AC10:ERK7 complex and its assembly into the cytoskeletal IMC, which serves as a structural scaffold that concentrates ERK7 kinase activity in the apical cap.

IMPORTANCE

The phylum Apicomplexa consists of obligate, intracellular parasites including the causative agents of toxoplasmosis, malaria, and cryptosporidiosis. Hallmarks of these parasites are the IMC and the apical complex, both of which are unique structures that are conserved throughout the phylum and required for parasite survival. The apical cap portion of the IMC has previously been shown to stabilize the apical complex. Here, we expand on those studies to determine the precise protein-protein interactions of the apical cap complex that confer this essential function. We describe the multivalent nature of these interactions and show that the resulting protein oligomers likely tether ERK7 in the apical cap. This study represents the first description of the architecture of the apical cap at a molecular level, expanding our understanding of the unique cell biology that drives Toxoplasma infections.
An Antioxidant Polysaccharide from Ganoderma lucidum Induces Apoptotic Activity in Breast Cancer Cell Line
Authors: Uddin Pk Md. Moyen , Pervin Rumana , Biswas Mohammad Shahangir , Rahman Md. Matiar
Published: January 2022

The purpose of this study is to elucidate the apoptotic activity of Ganoderma lucidum polysaccharide (GLP) in a human breast cancer cell line MCF-7 in vitro. According to DPPH assay, GLP showed a good antioxidant (IC50 value is 202.4 μg/mL). Based on MTT assay, the results showed that GLP inhibits MCF-7 cells proliferation in a dose- and time-dependent manner (p<0.001). IC50 values of the cytotoxicity of GLP and doxorubin were 110.907 μg/mL and 58.206 μg/mL respectively. The results from the flow cytometry indicated that GLP could induce apoptotic activity through inducing the up-regulation of the Bax and Caspase-9 and the down-regulation of the BcL-2 in MCF-7 cells. At 2×IC50, GLP increased the early-apoptotic and dead cells of MCF-7 from 18.23% to 34.76% and 8.45% to16.34% respectively. In conclusion, the GLP shows anticancer activity against MCF-7 through preventing the proliferation and inducing the apoptosis of MCF-7 cells. Our data provide the potential molecular targets in cancer prevention and reveal the key barriers in the current anticancer drugs development.
Sequence assignment validation in cryo-EM models with checkMySequence
Authors: Chojnowski Grzegorz
Published: January 2022

The availability of new AI-based protein structure prediction tools radically changed the way cryo-EM maps are interpreted, but it has not eliminated the challenges of map interpretation faced by a microscopist. Models will continue to be locally rebuilt and refined using interactive tools. This inevitably results in occasional errors, among which register-shifts remain one of the most difficult to identify and correct. Here we introduce checkMySequence; a fast, fully automated and parameter-free method for detecting register-shifts in protein models built into cryo-EM maps. We show that the method can assist model building in cases where poorer map resolution hinders visual interpretation. We also show that checkMySequence could have helped avoid a widely discussed sequence register error in a model of SARS-CoV-2 RNA-dependent RNA polymerase that was originally detected thanks to a visual residue-by-residue inspection by members of the structural biology community.

Synopsis

We present a new method, checkMySequence, for fast and automated detection of register errors in protein models built into cryo-EM reconstructions.
Embracing enzyme promiscuity with activity-based compressed biosensing
Authors: Holt Brandon Alexander , Lim Hong Seo , Su Melanie , Tuttle McKenzie , Liakakos Haley , Qiu Peng , Kwong Gabriel A.
Published: January 2022

Genome-scale activity-based profiling of proteases requires identifying substrates that are specific to each individual protease. However, this process becomes increasingly difficult as the number of target proteases increases because most substrates are promiscuously cleaved by multiple proteases. We introduce a method – Substrate Libraries for Compressed sensing of Enzymes (SLICE) – for selecting complementary sets of promiscuous substrates to compile libraries that classify complex protease samples (1) without requiring deconvolution of the compressed signals and (2) without the use of highly specific substrates. SLICE ranks substrate libraries according to two features: substrate orthogonality and protease coverage. To quantify these features, we design a compression score that was predictive of classification accuracy across 140 in silico libraries (Pearson r = 0.71) and 55 in vitro libraries (Pearson r = 0.55) of protease substrates. We demonstrate that a library comprising only two protease substrates selected with SLICE can accurately classify twenty complex mixtures of 11 enzymes with perfect accuracy. We envision that SLICE will enable the selection of peptide libraries that capture information from hundreds of enzymes while using fewer substrates for applications such as the design of activity-based sensors for imaging and diagnostics.
Hypoxia-Induced Ethanol Production in Arabidopsis Root Apex Cells Affects Endocytic Vesicle Recycling and F-Actin Organisation
Authors: Kagenishi Tomoko , Baluška František , Yokawa Ken
Published: January 2022

Ethanol (EtOH) is a short-chain alcohol that is abundant in nature. EtOH is endogenously produced by plants under hypoxic conditions, and exogenously applied EtOH improves plant stress tolerance at low concentrations (<1%). However, no direct observations have shown how EtOH affects cellular events in plants. In intact Arabidopsis roots, 0.1% EtOH promoted reactive oxygen species production in root apex cells. EtOH also accelerated exocytic vesicle recycling and altered F-actin organisation, both of which are closely related to cell membrane properties. In addition to exogenous EtOH application, hypoxic treatment resulted in EtOH production in roots and degradation of the cross-wall actin cytoskeleton in root epidermal cells. We conclude that hypoxia-induced EtOH production affects endocytic vesicle recycling and associated signalling pathways.
Mutation in shoot-to-root mobile transcription factor, ELONGATED HYPOCOTYL 5, leads to low nicotine levels in tobacco
Authors: Singh Deeksha , Dwivedi Shambhavi , Sinha Hiteshwari , Singh Nivedita , Trivedi Prabodh Kumar
Published: January 2022

Tobacco remains one of the most commercially important crops due to the parasympathomimetic alkaloid nicotine used in cigarettes. Most genes involved in nicotine biosynthesis are expressed in root tissues; however, their light-dependent regulation has not been studied. We identified the ELONGATED HYPOCOTYL 5 homolog, NtHY5, fromNicotiana tabacumand demonstrated its role in nicotine biosynthesis. We report the development of CRISPR/Cas9-based mutant plants,NtHY5CR, and show down-regulation of the nicotine biosynthetic pathway, whereas NtHY5 overexpression (NtHY5OX) plants show the opposite effect. Grafting experiments using wild type,NtHY5CR,and NtHY5OX indicated that NtHY5 moves from shoot-to-root to regulate nicotine biosynthesis in the root tissue. We conclude that shoot HY5, directly or through enhancing expression of the HY5 in the root, promotes nicotine biosynthesis. The CRISPR/Cas9-based mutants developed, in this study; with low nicotine accumulation in leaves could help people to overcome their nicotine addiction and the risk of death from tobacco use.