bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum markers of bone turnover change in response to depletion and repletion of fruit and vegetable intake in adults: a 28‐wk single‐arm experimental feeding intervention
Authors: Cao Jay J. , Whigham Leah D. , Jahns Lisa A.
Published: June 2021

Data from controlled intervention trials are lacking to support observational evidence suggesting a positive association between intake of fruit and vegetable (FV) and bone health. The objective of this study was to assess serum markers of bone turnover change in response to FV depletion and repletion. Twenty‐nine subjects participated in a 28‐wk single‐arm experimental feeding intervention trial and consumed low FV diets for 6 wks (depletion phases 1 and 3), a provided high FV diet based upon the Dietary Guidelines for Americans for 8 wks (6‐cup equivalents, phase 2), and usual diet for 8 wks (phase 4). At baseline, phases 1, 2, 3, and 4, intakes of total carotenoids, the most commonly used biomarker of FV intake, were 11.5 ± 1.2, 1.4 ± 0.2, 62.3 ± 0.9, 1.5 ± 0.4, and 9.0 ± 1.0 mg/d (mean ± SE), respectively, and the calculated dietary potential renal acid loads, a measure of the acid‐base load of foods, were 19.5 ± 4.6, −16.7 ± 5.3, 20.9 ± 2.8, 21.1 ± 2.8, and 14.2 ± 3.5 mEq/d, respectively. Compared to the baseline, depletion in FV intake (phase 1) resulted in an increase (p < 0.05) in serum C‐terminal telopeptide of type 1 collagen (CTX, 0.68 ± 0.05 vs 0.97 ± 0.08 ng/ml, respectively), a bone resorption marker, and a decrease in serum bone specific alkaline phosphatase (BALP, 10.7 ±0.7 vs 9.5 ± 0.8 μg/L, respectively), a bone formation maker. High FV intake (phase 2) decreased serum CTX (p < 0.05) to 0.60 ± 0.04 ng/ml and increased serum BALP to 11.3 ± 0.7μg/L (p < 0.05), compared to the depletion phase 1. These data demonstrate that increased fruit and vegetable consumption at or above federal dietary guidance is beneficial to bone health potentially through decreased dietary acidity.

Support or Funding Information

The study was supported by USDA ARS Current Research Information System no. 3062‐51000‐053‐00D and no. 3062‐51000‐051‐00D.
Structure and activity relationship of curucmin: role of methoxy group in anti‐inflammatory and anti‐colitis effects of curcumin
Authors: Yang Haixia , Du Zheyuan , Wang Weicang , Sanidad Katherine , Zhang Guodong
Published: June 2021

Substantial studies have shown that curcumin, a dietary compound from Turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease (IBD). A better understanding of structure‐activity relationship (SAR) of curcumin could help us to apprehend its molecular mechanism, and design better curcumin‐based drugs. While most previous studies have focused on the thiol‐reactive α,β‐unsaturated carbonyl groups of curcumin, little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogs with different substitution groups (R = H‐, Br‐, Cl‐, F‐, NO2‐, CH3‐, and OH‐) to replace the methoxy group, and evaluated their biological effects on inflammatory responses and NF‐κB signaling in RAW 264.7 macrophage cells, and dextran sulfate sodium (DSS)‐induced colitis in C57BL/6 mice. The analogs have dramatically different effects on inflammation in vitro and in vivo, supporting that the substitution group on the methoxy position plays an important role in the anti‐inflammatory effects of curcumin. The methoxy group is a potential structural candidate to modify, in order to design curcumin‐based drugs for inflammatory diseases.

Support or Funding Information

new faculty start‐up fund, Armstrong Fund of Science Award from University of Massachusetts Amherst and USDA NIFA 2016‐67017‐24423
Intranasal Oxytocin Reduces Cocaine Conditioned Locomotion and Anxiety‐like Behaviors due to a Cross‐talk with the Endocannabinoid System within the Mesolimbic System
Authors: Molina‐Castro Gian Carlo , Figueroa‐González Almaris , Loyola‐Vélez Alejandro , Marti‐Mendoza Amanda , Torres‐Hernández Edgardo , Maldonado‐Vlaar Carmen Sara
Published: June 2021

Oxytocin (OT) is a neuropeptide secreted by the hypothalamic paraventricular nucleus (PVN) and commonly associated with social behaviors, stress responses and drug‐addiction. Previous studies have shown that OT has anxiolytic properties associated with cues in a cocaine‐conditioning paradigm, but the underlying mechanism remains unknown. This study aims to characterize possible mechanistic interactions between OT and the endocannabinoid system mediating cocaine conditioning and anxiety response, in particular the cannabinoid receptor type 1 (CB1). Rats were exposed to activity chambers after receiving systemic intraperitoneal injections of cocaine (10 mg/kg) or saline 0.9%. during five consecutive days. On the testing session (D7), rats received intranasal infusions of OT (1 μg/μL) or vehicle (saline 0.9%) 30 minutes prior being exposed to the cue‐associated environment. Our results showed that OT pretreatment reduced both cocaine‐paired conditioned locomotion and anxiety‐like behaviors. Preliminary immunohistochemical analysis showed a colocalization of OT receptors and CB1 receptors within the nucleus accumbens (NAc) and the pre‐frontal cortex (PFC) in all treated animals. However, colocalization is pronounced when animals received intranasal OT pretreatment. The proposed mechanism includes a cross‐talk between OT and endocannabinoid system within mesolimbic system that might be responsible for the anxiety modulation triggered by cocaine exposure. This preliminary data suggests intranasal OT as a novel therapeutic approach of cocaine addiction.

Support or Funding Information

NIH BP‐ENDURE Neuro‐ID Program ‐ University of Puerto Rico‐Rio Piedras Campus (1R25MH092912‐01); RCMI Program (G12 MD007600); Nikon A1 Confocal Microscope (NSF DBI‐1337284); Dr. Manuel Díaz and Dr. Amelia Merced, Institute of Neurobiology, University of Puerto Rico‐Medical Sciences Campus
Gender Differences in Use of Social Media for Health‐related Information
Authors: Allison Chelsea , Wiggins Sa'Nealdra , Yan Wangcheng , Zhou Wenjun , Olfert Melissa D , Kattelmann Kendra , Mathews Anne , Brown Onikia , Kidd Tandalayo , Horacek Tanya , White Adrienne , Colby Sarah
Published: June 2021

BACKGROUND

Social media may be a useful tool in modifying health‐related behaviors; however, there is limited research on college students' use of health‐related social media and whether those behaviors vary by gender.

METHODS

Incoming first year students at eight universities were invited to complete screening surveys to determine if they were eligible to participate in Get Fruved, a study designed to decrease risk for unwanted weight gain. Eligible students (n=857) completed extensive health surveys and anthropometric measurements. Surveys included questions on social media usage and demographics. Pearson's Chi‐square tests were used to find differences in use of social media by gender.

RESULTS

Most participants (76.2% of females and 51.0% of males) reported they used social media to find health‐related information at least a couple of times a month, but only 10.2% of females and 4.4% of males reported using it more than four times per week. Increased time spent on social media was associated with increased use of social media to find health‐related information (p = .050) and reporting that social media impacted their view of nutrition (p = .017). Females were more likely than men to spend more time on social media (p = .003), use social media to find health‐related information (p < .001), and to report that social media impacted their view of nutrition (p < .001).

CONCLUSION

Researchers need to determine if exposing college students to health‐related social media will influence behavior differently by gender.

Support or Funding Information

This abstract is based upon work that is supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2014‐67001‐21851.
Alcohol Regulation of BK Channels Surface Expression via Beta‐Catenin Signaling
Authors: Garcia Jose Orlando , Burgos Alexandra , Soto Jessica , Cordero Katherine , Treistman Steven , Velazquez‐Marrero Cristina
Published: June 2021

Alcohol tolerance development and retention has long been associated to neural mechanisms related to learning and memory. We have found a persistent component of alcohol molecular tolerance; internalization of BK channels, in both striatal and hippocampus neurons. It is further characterized by increases in β‐catenin in response to physiologically relevant concentrations of alcohol, which are necessary for BK channel internalization. Accumulation of β‐catenin was impaired in the presence of general protein synthesis inhibitors cyclohexamide and emetine, which further blocked ethanol‐induced BK channel internalization in heterologous expression system. Interestingly, BK channel dissociation from lipid raft fractions in response to ethanol exposure was not significantly affected by protein synthesis inhibition. Translational regulation of EtOH was evaluated via tandem mass spectrometry (MS/MS) and Western Blot analysis of de novo synthesized proteins in heterologously expressed hSloα HEK293 preparations. Results indicated that β‐catenin is increased 2.5 fold in response to alcohol compared within a subset of over seven hundred proteins assayed. Transcriptional regulation of EtOH in striatal tissue has been further studied suggesting changes in miRNA profile in response to duration of EtOH exposure. These findings suggest the canonical Wnt/β‐catenin signaling pathway plays a critical role in mediating a persistent form of BK channel molecular alcohol tolerance regulating BK channel surface distribution, and potentially mediating transcriptional regulation in response to EtOH.

Support or Funding Information

This work was supported by the COBRE project grant 5P20GM103642 (CV‐M), Imaging core at the Institute of Neurobiology: NSF Grant DBI‐0115825 and DoD Grant 52680‐LS‐IS, Research infrastructure support was provided in part by a grant from the National Institute of Minority Health and Health Disparities (G12MD 007600), and USDE Title V Cooperative Agreement grant P031S130068 (JOG).
Metabolic Profiling and Physiological Monitoring in Hibernating Arctic Ground Squirrels during Ammonium Acetate Infusions
Authors: Rice Sarah A , D'Alessandro Angelo , Drew Kelly L
Published: June 2021

Hibernators such as the arctic ground squirrel, undergo periods of prolonged torpor interrupted by brief periods of euthermy (interbout arousals) throughout the hibernation season. Animals do not eat for the duration of the hibernation season that can last up to eight months in the arctic ground squirrel. In the last 10 years high throughput metabolic screenings of hibernators have elucidated key characteristics of different stages within the hibernation season, but this characterization has been limited to observational studies. Evidence suggests that interbout arousals function to maintain or rebalance carbon and nitrogen homeostasis. How nitrogen load impacts metabolic and neural signaling pathways during prolonged torpor is unknown. To define how physiologically relevant nitrogen loads impact the hibernation metabolic profile and onset of interbout arousal we infused a nitrogen donor during early torpor to mimic aspects of late‐stage torpor. Arctic ground squirrels were instrumented with indwelling arterial and venous cannulas and body temperature transmitters. The rate of oxygen consumption was monitored using open flow respirometry. Blood samples were collected for up to 10 days and analyzed by UHPLC‐MS. Infusion of ammonium acetate increased plasma glutamine and 5‐oxoproline levels significantly. This raises the interesting question about a potential role of the gamma‐glutamyl system in nitrogen balance and metabolic homeostasis in hibernation. This work was performed in conformance with the FASEB Statement of Principles for animals used in research.

Support or Funding Information

This work was supported by NSF IOS‐1258179
Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer
Authors: Igarashi Chika , Yoshii Yukie , Tashima Hideaki , Iwao Yuma , Sakurai Kohei , Hihara Fukiko , Tachibana Tomoko , Yoshida Eiji , Wakizaka Hidekatsu , Akamatsu Go , Yamaya Taiga , Yoshimoto Mitsuyoshi , Matsumoto Hiroki , Zhang Ming-Rong , Nagatsu Kotaro , Sugyo Aya , Tsuji Atsushi B. , Higashi Tatsuya
Published: June 2021

Background

In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called ‘OpenPET’), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery.

Methods

A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations.

Results

Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3–10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group.

Conclusions

OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.
Lipids and peripheral neuropathy
Authors: Iqbal Zohaib , Bashir Bilal , Ferdousi Maryam , Kalteniece Alise , Alam Uazman , Malik Rayaz A. , Soran Handrean
Published: June 2021

Purpose of review

Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy.

Recent findings

A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels.

Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.
The View From Here
Authors: Urban Regina Wilder , Brandenburg Lexi
Published: June 2021

This qualitative study is based on individual interviews with 16 new graduate nurses during their 8th to 10th month of employment. Four themes emerged from the data that reflected their lived experience: well on my way, finding my family, good days/bad days, and in recovery…moving forward. Nursing professional developers play an important role in continuing to support new graduate nurses to complete the transition to practice.
Virtual Simulation to Reinforce Nursing Staff Resuscitation Responses
Authors: Brzozowski Sara , Kandrack Margo , Oermann Marilyn H. , Dangerfield Cristie , Simmons (Muckler) Virginia C.
Published: June 2021

In-hospital cardiac arrests have high mortality rates, increased by delayed resuscitation. Using a single group pre–post interventional design to implement virtual cardiac arrest simulations for medical-surgical units, the purpose of this project was to decrease resuscitation delays and improve self-confidence of the nursing staff. Both response times and confidence improved following virtual simulation. Conducting virtual simulation for resuscitation training may be a valuable alternative to in situ simulation.
Sildenafil Citrate Overdose in a 3-Month Postterm Premature Infant With Pulmonary Artery Hypertension
Authors: van Heugten Marjolein , van Onzenoort-Bokken Lonneke
Published: June 2021

Objective

We aimed to describe a case of prematurely born infant with accidental sildenafil overdose.

Methods

This was a retrospective case report followed with chart and literature review.

Main Findings

A prematurely born infant with moderate bronchopulmonary dysplasia, corrected congenital heart disease, and pulmonary hypertension presented with an accidental sildenafil overdose. Despite the relatively high dose in this medically frail infant and the long elimination half-life of sildenafil in infants, the symptoms of sildenafil overdose in our patient were only mild. After a short and uneventful period of observation in the hospital, the patient was discharged home.

Conclusions

Sildenafil overdose can cause serious symptoms such as hypotension. However, in our case, the sildenafil overdose was well tolerated, even by a young patient with underlying heart and lung disease. We show that choices in the management of sildenafil intoxication can be made based on the knowledge of sildenafil pharmacokinetics in young children.
Objective and Subjective Perspectives on Implementation of a Violence Risk Screening Program in an Emergency Department
Authors: ROATEN KIMBERLY , BROWNE SABRINA , POLLIO DAVID E. , KHAN FUAD , NORTH CAROL S.
Published: June 2021

Objective:

The objective of this study was to use quantitative and qualitative data to gather information about emergency medicine and psychiatric provider perspectives regarding the evolution of a violence risk screening process including the simultaneous implementation of a universal suicide screening program.

Methods:

A retrospective review of violence risk screening data for 496 patient encounters over a 2-year period and across 4 phases of implementation and improvement was completed. Four focus groups were conducted with emergency medicine and psychiatric providers using nondirective facilitation methods to gather data regarding provider perspectives about violence and suicide risk screening. The focus groups were recorded, transcribed, and analyzed for thematic content.

Results:

Four of the 6 violence risk screening items were most strongly associated with high-risk stratification across all phases. There were no changes in proportions of positive responses for 3 of the items. The proportion of positive responses for the other items changed significantly after expert feedback and clarification of item wording. Only 3% of the focus group passages included discussion of the universal suicide screening program.

Conclusions:

The providers indicated that they believed the violence risk screening and suicide screening procedures helped improve clinical thoroughness and documentation. Ongoing feedback between providers and program developers was beneficial. The implementation of the universal suicide screening process was relatively seamless for these providers.
Perception of infection: disease-related social cues influence immunity in songbirds
Authors: Love Ashley C. , Grisham Kevin , Krall Jeffrey B. , Goodchild Christopher G. , DuRant Sarah E.
Published: June 2021

While avoidance of sick conspecifics is common among animals, little is known about how detecting diseased conspecifics influences an organism's physiological state, despite its implications for disease transmission dynamics. The avian pathogenMycoplasma gallisepticum(MG) causes obvious visual signs of infection in domestic canaries (Serinus canaria domestica), including lethargy and conjunctivitis, making this system a useful tool for investigating how the perception of cues from sick individuals shapes immunity in healthy individuals. We tested whether disease-related social information can stimulate immune responses in canaries housed in visual contact with either healthy or MG-infected conspecifics. We found higher complement activity and higher heterophil counts in healthy birds viewing MG-infected individuals around 6–12 days post-inoculation, which corresponded with the greatest degree of disease pathology in infected stimulus birds. However, we did not detect the effects of disease-related social cues on the expression of two proinflammatory cytokines in the blood. These data indicate that social cues of infection can alter immune responses in healthy individuals and suggest that public information about the disease can shape how individuals respond to infection.
Characterization and profiling of bacteriocin-like substances produced by lactic acid bacteria from cheese samples
Authors: Afrin Sadia , Hoque Mohammad Amirul , Sarker Ashish Kumar , Satter Mohammed A , Bhuiyan Mohammad Nazrul Islam
Published: June 2021

Bacteriocins have become biological weapons against harmful food pathogens and have attracted interest as tools for biopreservation. The aim of this study was to isolate, identify and characterize lactic acid bacterial (LAB) strains from cheese samples, partially purify potential bacteriocins and characterize their antimicrobial activity against pathogens. Bacteriocin-producing organisms were screened by Agar spot assay test. Initially, 25 LAB isolates were isolated from the cheese samples and identified as Lactobacillius spp., among them five strains were able to produce bacteriocin whose antimicrobial activates were analysed by agar-well-diffusion assay test against pathogenic organisms.

Bacillus subtilis

,

Bacillus cereus

,

Staphylococcus aureus

, Streptococcus thermophillus and Listeria monocytogens were inhibited, while

Enterococcus faecalis

,

Salmonella typhi

,

Escherichia coli

and

Pseudomonas aeruginosa

were resistant to the antimicrobial substances from LAB isolates. For optimal production of bacteriocin, LAB broth cultures were harvested at exponential phase. The molecular weights of the bacteriocins are between 7.0–15.0 kDa. The bacteriocins were characterized on the basis of their sensitivity to heat, pH, enzymes, NaCl and treatments with organic solvents. These results revealed that the bacteriocins from Lactobacillius spp. isolated from the cheese might have potential antimicrobial properties and give new insight in the development of bio-preservative agents to prevent and control pathogenic bacterial infection.
A Meta-Analysis of Mental Health among Latino Adults: Elucidating Disparities from Differences
Authors: Flórez Karen R. , Abbu Kyra Alyssa C. , Hossain Fariha , Wills Aprielle , Breslau Joshua
Published: June 2021

Latinos continue to experience disparities in access to treatment for mental health, and these appear to be worsening with time. This meta-analysis identified and compared studies (N=20): (1) Across Latino origin groups, (2) Across immigration-related characteristics, and (3) with non-Latino groups. For the first comparison, results consistently showed Puerto Ricans had the highest rate of utilization compared to their Mexican, Cuban, Central American, and Other counterparts. For the second comparison, U.S-born Latinos had higher utilization and mental health costs for services, as well as higher rate of depression/anxiety symptomatology compared to their immigrant counterparts. For the third comparison, results were not as consistent but trended towards lower/less rates by Latinos compared to non-Latino whites. More research is needed on the different Latino groups and across the acculturation spectrum if we are to understand disparities from differences in risk and service use among this heterogeneous group.
Across-animal odor decoding by probabilistic manifold alignment
Authors: Herrero-Vidal Pedro , Rinberg Dmitry , Savin Cristina
Published: June 2021

Identifying the common structure of neural dynamics across subjects is key for extracting unifying principles of brain computation and for many brain machine interface applications. Here, we propose a novel probabilistic approach for aligning stimulus-evoked responses from multiple animals in a common low dimensional manifold and use hierarchical inference to identify which stimulus drives neural activity in any given trial. Our probabilistic decoder is robust to a range of features of the neural responses and significantly outperforms existing neural alignment procedures. When applied to recordings from the mouse olfactory bulb, our approach reveals low-dimensional population dynamics that are odor specific and have consistent structure across animals. Thus, our decoder can be used for increasing the robustness and scalability of neural-based chemical detection.
Exploring the Self-Assembly of Encapsulin Protein Nanocages from Different Structural Classes
Authors: Boyton India , Goodchild Sophia C. , Diaz Dennis , Elbourne Aaron , Collins-Praino Lyndsey , Care Andrew
Published: June 2021

Encapsulins, self-assembling icosahedral protein nanocages derived from prokaryotes, represent a versatile set of tools for nanobiotechnology. However, a comprehensive understanding of the mechanisms underlying encapsulin self-assembly, disassembly, and reassembly is lacking. Here, we characterise the disassembly/reassembly properties of three encapsulin nanocages that possess different structural architectures:T= 1 (24 nm),T= 3 (32 nm), andT= 4 (42 nm). Using spectroscopic techniques and electron microscopy, encapsulin architectures were found to exhibit varying sensitivities to the denaturant guanidine hydrochloride (GuHCl), extreme pH, and elevated temperature. While all encapsulins showed the capacity to reassemble following GuHCl-induced disassembly (within 75 min), only the smallestT= 1 nanocage reassembled after disassembly in basic pH (within 15 min). Furthermore, atomic force microscopy revealed that all encapsulins showed a significant loss of structural integrity after undergoing sequential disassembly/reassembly steps. These findings provide insights into encapsulins’ disassembly/reassembly dynamics, thus informing their future design, modification, and application.
Study of growth characteristics of callus, suspension and root crops Scutellaria baicalensis
Authors: Dmitrieva Anastasia Igorevna , Fedorova Anastasia Michailovna , Le Violetta Mironovna
Published: June 2021

Scutellaria baicalensis is a popular traditional plant in Chinese medicine. Widely distributed biologically active substances of Scutellaria baicalensis are flavonoids (baicalin, baicalein, vogonin and vogonoside), which are responsible for the antitumor activity. Their antitumor effect is due to the absorption of oxidative radicals, the weakening of the activity of NF-kB (nuclear factor-kB), the suppression of the expression of the COX-2 gene and the regulation of the cell cycle. In addition, baicalein, baicalin, and vogonin showed strong antioxidant activity. The root culture in vitro of the medicinal plant Scutellaria baicalensis is characterized by intensive growth. The growth index at the end of the cultivation cycle was 40. The growth curve has a standard S-shape, with pronounced growth phases. The stationary phase was observed from 5-7 weeks of cultivation. The root culture growth index was 22.
Seroprevalence of SARS-CoV-2 Antibodies Among Rural Healthcare Workers
Authors: Neises Jordan Z. , Hossain Md Saddam , Sultana Rifat , Wanniarachchi Kevin N. , Wollman Jared W. , Nelson Eric , Specker Bonny L. , Hoppe Adam D. , Lawson Steven R. , Thiex Natalie W.
Published: June 2021

The objective of this longitudinal cohort study was to determine the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in healthcare workers employed at healthcare clinics in three rural counties in eastern South Dakota and western Minnesota from May 13, 2020 through December 22, 2020. Three blood draws were performed at five clinical sites and tested for the presence of antibodies against the SARS-CoV-2 virus. Serum samples were tested for the presence of antibodies using a fluorescent microsphere immunoassay (FMIA), neutralization of SARS-CoV-2 Spike-pseudotyped particles (SARS-CoV-2pp) assay, and serum virus neutralization (SVN) assay. The seroprevalence was determined to be 1/336 (0.29%) for samples collected from 5/13/20-7/13/20, 5/260 (1.92%) for samples collected from 8/13/20-9/25/20, and 35/235 (14.89%) for samples collected from 10/16/20-12/22/20. Eight of the 35 (22.8%) seropositive individuals identified in the final draw did not report a previous diagnosis with COVID-19. There was a high correlation (>90%) among the FMIA and virus neutralization assays. Each clinical site’s seroprevalence was higher than the cumulative incidence for the general public in each respective county as reported by state public health agencies. As of December 2020, there was a high percentage (85%) of seronegative individuals in the study population.
Establishing the causal role of intimate partner violence and abuse on depressive symptoms in young adults: a population-based cohort study
Authors: Herbert Annie , Heron Jon , Barnes Maria , Barter Christine , Feder Gene , Meghrawi Khadija , Szilassy Eszter , Fraser Abigail , Howe Laura D
Published: June 2021

Background

Previous studies have shown an association between experience of intimate partner violence and abuse (IPVA) and depression. Whether this is a causal relationship or explained by prior vulnerability that influences the risk of both depression and IPVA is not known.

Methods and Findings

We analysed data from the Avon Longitudinal Study of Parents and Children prospective cohort (N=1,764 women, 1,028 men). To assess the causal association between IPVA at 18-21 years old and logged depressive symptom scores at age 23, we used: i) multivariable linear regression, ii) inverse probability of treatment weighting (IPTW), and iii) difference-in-difference (DID) analysis, which compared the mean change in logged depressive symptom scores between ages 16 and 23 between those who experienced IPVA and those who did not.

Women who experienced IPVA had on average 26% higher depressive symptom score after adjustment for measured confounders (ratio of geometric means 1.26, 95% CI 1.13 to 1.40). In men, the difference was 5% (ratio of geometric means 1.05, 95% CI 0.92 to 1.21). Results from IPTW analysis were similar. In the DID analysis, there was no evidence that being exposed to IPVA affected the change in depressive symptom scores over time compared to being in the non-exposed group for either women (difference-in-differences: 1%, -12% to 16%) or men (−1%, -19% to 20%).

Conclusions

Multivariable linear regression and IPTW suggested an association between IPVA and higher depressive symptom score in women but not men, but DID analysis indicated a null effect in both women and men. This suggests the causal origins of higher depressive symptoms in this young adult population are likely to reflect prior vulnerability that leads to both higher depressive symptoms and increased risk of IPVA exposure.

Key messages

Women and, to a lesser degree, men who experience IPVA between the ages of 18-21 years old tend to have higher levels of depressive symptoms at age 23 years than people who do not.

In women, the association between IPVA and higher depressive symptoms remained after adjustment for measured confounders or use of inverse probability of treatment weighting, whereas in men, the association attenuated to the null after adjustment for measured confounders or use of inverse probability of treatment weighting.

However, the change in depressive symptoms between ages 16 and 23 years was the same in people who experience IPVA and people who did not, for both women and men. This suggests that the higher levels of depressive symptoms in people who experience IPVA is likely to be driven by prior vulnerability that affects the risk of both IPVA exposure and depressive symptoms, highlighting that IPVA is one of a series of challenges being navigated by psychologically vulnerable young adults.
Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: A scoping review
Authors: Bennett Alexandria , Crosse Kien , Ku Michael , Edgar Nicole E. , Hodgson Amanda , Hatcher Simon
Published: June 2021

Objectives

The goals of this study are to identify and analyse interventions that aim to treat Post Traumatic Stress Disorder (PTSD) and complex PTSD in individuals who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care.

Design

Scoping review

Search strategy

We searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science, and PTSDpubs for published literature up to March 2020 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organizations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analyzed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described.

Results

26 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions; and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomized controlled trials, were generally ineffective. Of the ten studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover.

Conclusions

This scoping review identified a lack of high-quality trials to address PTSD in the vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.

Strengths and limitations of this study

First review of how trauma-informed care is being operationalized in the treatment of PTSD for the vulnerably housed.

Provides a clear picture emphasizing the need to consistently utilize a trauma-informed care approach for PTSD treatment in the vulnerably housed.

Largely homogenous populations (primarily women and US Veterans) included in studies, may not be representative of broader population.

Often no mention of ethnic or cultural factors to consider when providing treatment.

Many of the studies available were of low methodological quality.
Towards a Comprehensive Variation Benchmark for Challenging Medically-Relevant Autosomal Genes
Authors: Wagner Justin , Olson Nathan D , Harris Lindsay , McDaniel Jennifer , Cheng Haoyu , Fungtammasan Arkarachai , Hwang Yih-Chii , Gupta Richa , Wenger Aaron M , Rowell William J , Khan Ziad M , Farek Jesse , Zhu Yiming , Pisupati Aishwarya , Mahmoud Medhat , Xiao Chunlin , Yoo Byunggil , Sahraeian Sayed Mohammad Ebrahim , Miller Danny E. , Jáspez David , Lorenzo-Salazar José M. , Muñoz-Barrera Adrián , Rubio-Rodríguez Luis A. , Flores Carlos , Narzisi Giuseppe , Evani Uday Shanker , Clarke Wayne E. , Lee Joyce , Mason Christopher E. , Lincoln Stephen E. , Miga Karen H. , Ebbert Mark T. W. , Shumate Alaina , Li Heng , Chin Chen-Shan , Zook Justin M , Sedlazeck Fritz J
Published: June 2021

The repetitive nature and complexity of multiple medically important genes make them intractable to accurate analysis, despite the maturity of short-read sequencing, resulting in a gap in clinical applications of genome sequencing. The Genome in a Bottle Consortium has provided benchmark variant sets, but these excluded some medically relevant genes due to their repetitiveness or polymorphic complexity. In this study, we characterize 273 of these 395 challenging autosomal genes that have multiple implications for medical sequencing. This extended, curated benchmark reports over 17,000 SNVs, 3,600 INDELs, and 200 SVs each for GRCh37 and GRCh38 across HG002. We show that false duplications in either GRCh37 or GRCh38 result in reference-specific, missed variants for short- and long-read technologies in medically important genes including CBS, CRYAA, and KCNE1. Our proposed solution improves variant recall in these genes from 8% to 100%. This benchmark will significantly improve the comprehensive characterization of these medically relevant genes and guide new method development.
PALB2 maintains redox and mitochondrial homeostasis in the brain and cooperates with ATG7 to suppress p53 dependent neurodegeneration
Authors: Huo Yanying , Sawant Akshada , Tan Yongmei , Mahdi Amar H , Li Tao , Ma Hui , Bhatt Vrushank , Yan Run , Coleman Jake , Dreyfus Cheryl F. , Guo Jessie Yanxiang , Mouradian M. Maral , White Eileen , Xia Bing
Published: June 2021

The PALB2 tumor suppressor plays key roles in DNA repair and has been implicated in redox homeostasis. Autophagy maintains mitochondrial quality, mitigates oxidative stress and suppresses neurodegeneration. Here we show that Palb2 deletion in the mouse brain leads to motor deficits and that co-deletion of Palb2 with the essential autophagy gene Atg7 accelerates and exacerbates neurodegeneration induced by ATG7 loss. Palb2 deletion leads to elevated DNA damage, oxidative stress and mitochondrial markers, especially in Purkinje cells, and co-deletion of Palb2 and Atg7 results in accelerated Purkinje cell loss. Further analyses suggest that the accelerated Purkinje cell loss and severe neurodegeneration in the double deletion mice are due to oxidative stress and mitochondrial dysfunction, rather than DNA damage, and partially dependent on p53 activity. Our studies uncover a role of PALB2 in mitochondrial regulation and a cooperation between PALB2 and ATG7/autophagy in maintaining redox and mitochondrial homeostasis essential for neuronal survival.
Variation in Human Herpesvirus 6B telomeric integration, excision and transmission between tissues and individuals
Authors: Wood M.L. , Veal C. , Neumann R. , Suárez N.M. , Nichols J. , Parker A.J. , Martin D. , Romaine S.P.R , Codd V. , Samani N.J. , Voors A.A. , Tomaszewski M. , Flamand L. , Davison A.J. , Royle N.J.
Published: June 2021

Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally- integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV- 6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms.
The local anaesthetic procaine prodrugs ProcCluster® and Procaine-hydrochloride impair SARS-CoV-2 replication in vitro
Authors: Häring Clio , Schroeder Josefine , Löffler Bettina , Engert Beatrice , Ehrhardt Christina
Published: June 2021

The SARS-CoV-2 pandemic has had the world in suspense for more than a year. Even if more and more vaccines are approved there is still an urgent need for efficient antiviral treatment strategies. Here, we present data on the inhibitory effect of the local anaesthetic procaine, especially the prodrugs ProcCluster® and Procaine-hydrochloride on SARS-CoV-2 infection in vitro. Remarkably, similar effects could be shown on the replication of influenza A viruses in cell culture systems. Since the active ingredient procaine is well-tolerated and already used in the clinics for anaesthetic purposes, the further investigation of this substance could enable its reuse in antiviral therapy, including SARS-CoV-2.
Natural variation in theirldgene family affects starvation resistance inC. elegans
Authors: Webster Amy K. , Chitrakar Rojin , Powell Maya , Chen Jingxian , Fisher Kinsey , Tanny Robyn , Stevens Lewis , Evans Kathryn , Wei Angela , Antoshechkin Igor , Andersen Erik C. , Baugh L. Ryan
Published: June 2021

Starvation resistance is important to disease and fitness, but the genetic basis of its natural variation is unknown. We developed a synthetic-population (re)sequencing approach using molecular inversion probes (MIP-seq) to measure relative fitness during and after larval starvation inC. elegans. We applied this competitive assay to 100 genetically diverse, sequenced, wild strains, revealing natural variation in starvation resistance. We confirmed that the most starvation-resistant strains survive and recover from starvation better than the most starvation-sensitive strain, MY2147, using standard assays. We performed genome-wide association with the MIP-seq trait data and identified three quantitative trait loci (QTL) for starvation resistance. These QTL contain several members of the Insulin/EGF Receptor-L Domain (irld) family with sequence variation associated with variation in starvation resistance. We used genome editing to show that individual modification of fourirldgenes increases starvation resistance of MY2147. Modification ofirld-39andirld-52together increases starvation resistance of the laboratory-reference strain N2. Increased starvation resistance of theirld-39; irld-52double mutant depends ondaf-16/FoxO, and these worms also show increased nuclear localization of DAF-16 during starvation. DAF-16/FoxO is a widely conserved transcriptional effector of insulin/IGF signaling (IIS), and these results suggest that IRLD proteins modify IIS. This work demonstrates efficacy of using MIP-seq to dissect a complex trait, identifiesirldgenes as natural modifiers of starvation resistance inC. elegans, and suggests that an expanded gene family affects a deeply conserved signaling pathway to alter a fitness-proximal trait.
RBPSpot: Learning on Appropriate Contextual Information for RBP Binding Sites Discovery
Authors: Sharma Nitesh Kumar , Gupta Sagar , Kumar Prakash , Kumar Ashwani , Pradhan Upendra Kumar , Shankar Ravi
Published: June 2021

Identifying RBP binding sites and mechanistic factors determining the interactions remain a big challenge. Besides the sparse binding motifs across the RNAs, it also requires a suitable sequence context for binding. The present work describes an approach to detect RBP binding sites while using an ultra-fast BWT/FM-indexing coupled inexact k-mer spectrum search for statistically significant seeds. The seed works as an anchor to evaluate the context and binding potential using flanking region information while leveraging from Deep Feed-forward Neural Network (DNN). Contextual features based on pentamers/dinucloetides which also capture shape and structure properties appeared critical. Contextual CG distribution pattern appeared important. The developed models also got support from MD-simulation studies and the implemented software, RBPSpot, scored consistently high for the considered performance metrics including average accuracy of ∼90% across a large number of validated datasets while maintaining consistency. It clearly outperformed some recently developed tools, including some with much complex deep-learning models, during a highly comprehensive bench-marking process involving three different data-sets and more than 50 RBPs. RBPSpot, has been made freely available, covering most of the human RBPs for which sufficient CLIP-seq data is available (131 RBPs). Besides identifying RBP binding spots across RNAs in human system, it can also be used to build new models by user provided data for any species and any RBP, making it a valuable resource in the area of regulatory system studies.