bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein folding stabilities are a major determinant of oxidation rates for buried methionine residues
Authors: Walker Ethan J. , Bettinger John Q. , Welle Kevin A. , Hryhorenko Jennifer R. , Molina Vargas Adrian M. , O’Connell Mitchell R. , Ghaemmaghami Sina 
Published: December 2021

AbstractThe oxidation of protein-bound methionines to form methionine sulfoxides has a broad range of biological ramifications, making it important to delineate factors that influence methionine oxidation rates within a protein. This is especially important for biopharmaceuticals, where oxidation can lead to deactivation and degradation. Previously, neighboring residue effects and solvent accessibility (SA) have been shown to impact the susceptibility of methionine residues to oxidation. In this study, we provide proteome-wide evidence that oxidation rates of buried methionine residues are also strongly influenced by the thermodynamic folding stability of proteins. We surveyed the E. coli proteome using several proteomic methodologies and globally measured oxidation rates of methionines in the presence and absence of tertiary structure, as well as folding stabilities of methionine containing domains. The data indicate that buried methionines have a wide range of protection factors against oxidation which correlate strongly with folding stabilities. Concordantly, we show that in comparison to E. coli, the proteome of the thermophile T. thermophilus is significantly more stable and thus more resistant to methionine oxidation. These results indicate that oxidation rates of buried methionines from the native state of proteins can be used as a metric of folding stability. To demonstrate the utility of this correlation, we used native methionine oxidation rates to survey the folding stabilities of E. coli and T. thermophilus proteomes at various temperatures and suggest a model that relates the temperature dependence of the folding stabilities of these two species to their optimal growth temperatures.
TSC22D4 interacts with Akt1 in response to metabolic and stress signals
Authors: Demir Sevgican , Wolff Gretchen , Wieder Annika , Maida Adriano , Rahm Marco , Schnölzer Martina , Hauck Stefanie , Szendrödi Julia , Herzig Stephan , Üstünel Bilgen Ekim 
Published: December 2021

AbstractTransforming Growth Factor β 1 Stimulated Clone 22 D4 (TSC22D4) is an intrinsically disordered protein that regulates cellular and physiological processes such as cell proliferation, cellular senescence as well as hepatic glucose and lipid metabolism. The molecular mechanism of TSC22D4 action in these cellular and metabolic functions, however, remains largely elusive. Here, we identified TSC22D4 as a novel protein kinase B/Akt1 interacting protein, a critical mediator of insulin/PI3K signaling pathway implicated in diverse set of diseases including type 2 diabetes, obesity and cancer. TSC22D4 interacts with Akt1 not constitutively but rather in a regulatory manner. While glucose and insulin stimulation of cells or refeeding of mice impair the hepatic TSC22D4-Akt1 interaction, inhibition of mitochondria and oxidative stress, promote it; indicating that extra- and intra-cellular cues play a key role in controlling TSC22D4-Akt1 interaction. Our results also demonstrate that together with its dimerization domain, i.e. the TSC box, TSC22D4 requires its intrinsically disordered region (D2 domain) to interact with Akt1. To understand regulation of TSC22D4 function further, we employed tandem mass spectrometry and identified 15 novel phosphorylation sites on TSC22D4. Similar to TSC22D4-Akt1 interaction, TSC22D4 phosphorylation also responds to environmental signals such as starvation, mitochondrial inhibition and oxidative stress. Interestingly, 6 out of the 15 novel phosphorylation sites lie within the TSC22D4 D2 domain, which is required for TSC22D4-Akt1 interaction. Characterization of the regulation and function of these novel phosphorylation sites, in the future, will shed light on our understanding of the role of TSC22D4-Akt1 interaction in both cell biological and physiological functions. Overall, our findings postulate a model whereby TSC22D4 acts as an environmental sensor and interacts with Akt1 to regulate cell proliferation, cellular senescence as well as maintain metabolic homeostasis.
Targeting RTN4/NoGo-Receptor reduces levels of ALS protein ataxin-2
Authors: Rodriguez Caitlin M. , Bechek Sophia C. , Jones Graham L. , Nakayama Lisa , Akiyama Tetsuya , Kim Garam , Solow-Cordero David E. , Strittmatter Stephen M. , Gitler Aaron D. 
Published: December 2021

SummaryGene-based therapeutic strategies to lower ataxin-2 levels are emerging for neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (SCA2). To identify additional ways of reducing ataxin-2 levels, we performed a genome-wide screen in human cells for regulators of ataxin-2 and identified RTN4R, the gene encoding the RTN4/NoGo-Receptor, as a top hit. RTN4R knockdown, or treatment with a peptide inhibitor, was sufficient to lower ataxin-2 protein levels in mouse and human neurons in vitro and Rtn4r knockout mice have reduced ataxin-2 levels in vivo. Remarkably, we observed that ataxin-2 shares a role with the RTN4/NoGo-Receptor in limiting axonal regeneration. Reduction of either protein increases axonal regrowth following axotomy. These data define the RTN4/NoGo-Receptor as a novel therapeutic target for ALS and SCA2 and implicate the targeting of ataxin-2 as a potential treatment following nerve injury.
Small molecule v-ATPase inhibitor Etidronate lowers levels of ALS protein ataxin-2
Authors: Kim Garam , Nakayama Lisa , Blum Jacob A. , Akiyama Tetsuya , Boeynaems Steven , Chakraborty Meena , Couthouis Julien , Tassoni-Tsuchida Eduardo , Rodriguez Caitlin M. , Bassik Michael C. , Gitler Aaron D. 
Published: December 2021

SummaryAntisense oligonucleotide therapy targeting ATXN2—a gene in which mutations cause neurodegenerative diseases spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis—has entered clinical trials in humans. Additional methods to lower ataxin-2 levels would be beneficial not only in uncovering potentially cheaper or less invasive therapies, but also in gaining greater mechanistic insight into how ataxin-2 is normally regulated. We performed a genome-wide fluorescence activated cell sorting (FACS)-based CRISPR screen in human cells and identified multiple subunits of the lysosomal vacuolar ATPase (v-ATPase) as regulators of ataxin-2 levels. We demonstrate that Etidronate—a U.S. Food and Drug Administration (FDA)-approved drug that inhibits the v-ATPase—lowers ataxin-2 protein levels in mouse and human neurons. Moreover, oral administration of the drug to mice in their water supply and food is sufficient to lower ataxin-2 levels in the brain. Thus, we uncover Etidronate as a safe and inexpensive compound for lowering ataxin-2 levels and demonstrate the utility of FACS-based screens for identifying targets to modulate levels of human disease proteins.
Recent trends in labor productivity
Authors: Salimova Guzel , Ableeva Alisa , Galimova Aygul , Bakirova Ramzilya , Lubova Tatiana , Sharafutdinov Aidar , Araslanbaev Irek 
Published: December 2021

PurposeUsing the example of Russia, this paper studied and analyzed productivity of the labor force in agriculture as an important industry for ensuring the sustainable development of the country.Design/methodology/approachAt the first examination stage, the time series of data on labor productivity and real wages in agri-food companies were examined as modern works on the matter tend to highlight the relationship between productivity and remuneration insufficiently. At the second stage, labor productivity was assessed through the rate of change in the share of wages in the gross domestic product. At the last stage, an applied model of the relationship between labor productivity in agriculture and various impact factors was developed.FindingsIt showed that the efficiency of the labor force in the considered area depends greatly on technical equipment and crop yield. Besides, the study findings revealed that the traditional economic relationship between productivity and wages is invalid in the examined regions of Russia. There is a significant reserve for increasing labor productivity by providing additional motivation for employees.Originality/valueThe successful development of agricultural production can be achieved by implementing innovations, facilitating digitalization, attracting investments, increasing the level of interest of those employed in labor results and producing high-quality goods.
Tornadoes, poverty and race in the USA: A five-decade analysis
Authors: Kashian Russ D. , Buchman Tracy , Drago Robert 
Published: December 2021

PurposeThe study aims to analyze the roles of poverty and African American status in terms of vulnerability to tornado damages and barriers to recovery afterward.Design/methodology/approachUsing five decades of county-level data on tornadoes, the authors test whether economic damages from tornadoes are correlated with vulnerability (proxied by poverty and African American status) and wealth (proxied by median income and educational attainment), controlling for tornado risk. A multinomial logistic difference-in-difference (DID) estimator is used to analyze long-run effects of tornadoes in terms of displacement (reduced proportions of the poor and African Americans), abandonment (increased proportions of those groups) and neither or both.FindingsControlling for tornado risk, poverty and African American status are linked to greater tornado damages, as is wealth. Absent tornadoes, displacement and abandonment are both more likely to occur in urban settings and communities with high levels of vulnerability, while abandonment is more likely to occur in wealthy communities, consistent with on-going forces of segregation. Tornado damages significantly increase abandonment in vulnerable communities, thereby increasing the prevalence of poor African Americans in those communities. Therefore, the authors conclude that tornadoes contribute to on-going processes generating inequality by poverty/race.Originality/valueThe current paper is the first study connecting tornado damages to race and poverty. It is also the first study finding that tornadoes contribute to long-term processes of segregation and inequality.
(Un)disclosed. Disease disclosure in people living with rheumatic diseases: An exploratory study
Authors: Ostuzzi Silvia Maria Teresa , Ingegnoli Francesca , Pistarini Caterina , Aiello Edoardo Nicolò , Fiabane Elena Maria 
Published: December 2021

AbstractObjectiveLittle is known about disease‐related disclosure (DD) in patients with rheumatic musculoskeletal diseases (RMDs). We aim to investigate DD behaviors and to explore which socio‐demographic, clinical and psychological factors play a role in this self‐disclosure process among patients with RMDs.MethodsA cross‐sectional Italian nationwide study captured DD in RMDs in different contexts (workplace, family, friends, partner, social networks). An ad hoc survey was developed and disseminated by the Patients' Association ALOMAR ODV (Lombard Association for Rheumatic Diseases) between June and July 2020. Patient demographics, clinical data, and questionnaires assessing anxiety, depression, anticipated stigma, patient health engagement, perceived social support, and perceived general health status were collected.ResultsThere were 376 rheumatic patients who completed the survey. There were 73.9% of the participants who talk to others about their RMD “sometimes”; 18.7% disclose their RMD “always/very often”, while 7.4% “never” talk about their RMD. A significant association was detected between DD and both perceived visibility (P = .04) and psychological support (P = .01). Moreover, participants who never/sometimes disclose their RMD reported significantly lower scores in the “Total” Social Support (P < .01) and in the “Friends” subscale (P < .001) compared to others. Psychological support and the “Friends” subscale were the only significant predictors of DD (both P = .002).ConclusionsThe majority of RMD patients disclosed their disease “sometimes”. The DD behavior is not associated with any specific demographic or clinical variables. Further research on the subject might help to foster better DD decision‐making processes for rheumatic patients in different contexts of daily life.
Primary hyperparathyroidism in adults—(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society
Authors: Milat Frances , Ramchand Sabashini K. , Herath Madhuni , Gundara Justin , Harper Simon , Farrell Stephen , Girgis Christian M. , Clifton‐Bligh Roderick , Schneider Hans G. , De Sousa Sunita M. C. , Gill Anthony J. , Serpell Jonathan , Taubman Kim , Christie James , Carroll Richard W. , Miller Julie A. , Grossmann Mathis 
Published: December 2021

AbstractObjectiveTo formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults.MethodsRepresentatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing nine key questions.ResultsPHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25‐hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk‐benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients.ConclusionsThese clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.
Long‐term monitoring of wildlife populations for protected area management in Southeast Asia
Authors: Nuttall Matthew N. , Griffin Olly , Fewster Rachel M. , McGowan Philip J. K. , Abernethy Katharine , O'Kelly Hannah , Nut Menghor , Sot Vandoeun , Bunnefeld Nils 
Published: December 2021

AbstractLong‐term monitoring of biodiversity in protected areas (PAs) is critical to assess threats, link conservation action to species outcomes, and facilitate improved management. Yet, rigorous longitudinal monitoring within PAs is rare. In Southeast Asia (SEA), there is a paucity of long‐term wildlife monitoring within PAs, and many threatened species lack population estimates from anywhere in their range, making global assessments difficult. Here, we present new abundance estimates and population trends for 11 species between 2010 and 2020, and spatial distributions for 7 species, based on long‐term line transect distance sampling surveys in Keo Seima Wildlife Sanctuary in Cambodia. These represent the first robust population estimates for four threatened species from anywhere in their range and are among the first long‐term wildlife population trend analyses from the entire SEA region. Our study revealed that arboreal primates and green peafowl (Pavo muticus) generally had either stable or increasing population trends, whereas ungulates and semiarboreal primates generally had declining trends. These results suggest that ground‐based threats, such as snares and domestic dogs, are having serious negative effects on terrestrial species. These findings have important conservation implications for PAs across SEA that face similar threats yet lack reliable monitoring data.
Where can you wear your Libre? Using the FreeStyle Libre continuous glucose monitor on alternative sites
Authors: Hall Rosemary M. , Dyhrberg Sophie , McTavish Arthur , McTavish Lindsay , Corley Brian , Krebs Jeremy D. 
Published: December 2021

AbstractAimTo investigate the accuracy and acceptability of the FreeStyle Libre Flash continuous glucose monitoring system (FSL‐CGM) at alternative sites during free living and under experimental conditions.Materials and MethodsParticipants with type 1 diabetes were provided with three FSL‐CGM sensors applied to the upper arm, the lower back, and the anterior chest. On day 2 or 3, FSL‐CGM sensor glucose was compared with venous glucose following a standard meal, during and after an exercise test, and after skin cooling. Participants completed 14‐day use of the sensors with concomitant sensor scanning at all sites and capillary glucose tests. The primary outcome was accuracy between sensor sites of 14‐day mean glucose. Clarke's error grids, precision absolute relative deviation, and mean absolute relative deviation were calculated.ResultsIn the 20 participants, compared with the arm sensor, the accuracy of the back sensor and the chest sensor was 97.9% and 98%, respectively. Under experimental conditions, the arm sensor was more accurate than that of the back and chest. All the sensors recorded higher glucose concentration than venous samples during exercise. The arm and chest sites were most preferred, with the greatest sensor failures from the back.ConclusionsThe FSL‐CGM is clinically accurate when the sensors are applied to alternate chest or back sites. Greater variability occurs during rapid changes in glucose concentration with all sensor sites compared with venous glucose. Understanding these variabilities allows appropriate use of an economically viable continuous glucose monitor.
miR‐24‐3p obstructs the proliferation and migration of human skin fibroblasts after thermal injury by targeting PPAR‐β and positively regulated by NF‐κB
Authors: Cui Xu , Huang Xu , Huang Mitao , Zhou Situo , Le Guo , Yu Wenchang , Duan Mengting , Jiang Bimei , Zeng Jizhang , Zhou Jie , Huang Xiaoyuan , Liang Pengfei , Zhang Pihong 
Published: December 2021

AbstractThermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR‐24‐3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR‐β protein expression level progressively increased in a time‐dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR‐β markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL‐6, TNF‐α, PTGS‐2 and P65 expression. PPAR‐β contrastingly exhibited an opposite trend. A targeted relationship between PPAR‐β and miR‐24‐3p was predicted and verified. miR‐24‐3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR‐β. p65 directly targeted the transcriptional precursor of miR‐24 and promoted miR‐24 expression. A negative correlation between miR‐24‐3p expression level and PPAR‐β expression level in rats’ burnt dermal tissues was observed. Our findings reveal that miR‐24‐3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns.
Toward tailored care for families with multiple problems: A quasi‐experimental study on effective elements of care
Authors: Visscher Loraine , Reijneveld Sijmen A. , Knot‐Dickscheit Jana , van Yperen Tom A. , Scholte Ron H.J. , Delsing Marc J.M.H. , Evenboer K. Els , Jansen Danielle E.M.C. 
Published: December 2021

AbstractSeveral effective interventions have been developed for families with multiple problems (FMP), but knowledge is lacking as to which specific practice and program elements of these interventions deliver positive outcomes. The aim of this study is to assess the degree to which practice and program elements (contents of and structure in which care is provided) contribute to the effectiveness of interventions for FMP in general and for subgroups with child and/or parental psychiatric problems, intellectual disabilities, or substance use. We performed a quasi‐experimental study on the effectiveness of practice and program elements provided in attested FMP interventions. Using self‐report questionnaires, we measured primary (child's internalizing and externalizing problems) and secondary (parental stress and social contacts) outcomes at the beginning, end, and three months thereafter. By means of Latent Profile Analysis, we identified groups of families receiving similar combinations of practice elements (“profiles”), and we calculated propensity scores. Next, we assessed how practice element profiles and program elements affected improvement in outcomes, and whether these effects were moderated by subgroup characteristics. We found three practice element profiles (explorative/supportive, action‐oriented, and their combination), which were equally effective. Regarding program elements, effects were enhanced by more frequent telephone contact between visits and more frequent intervision. Effectiveness of practice and program elements varied for specific FMP subgroups. Variations in the content of care for FMP do not affect its effectiveness, but variations in the structure of the care do. This finding can help to further improve effective interventions.
Fulton's flaw: In the constitutional clash between religious liberty and LGBTQ+ rights, foster kids are neither seen nor heard
Authors: Hicks Tanya Washington 
Published: December 2021

AbstractThis essay asserts the primacy of children's interests as a constitutional check on the religious liberty interests of government contractors that express in ways adverse to the best interests of foster children harmed by discriminatory foster care screening processes. The piece begins with an examination of child welfare realities characterized by increasing numbers of foster children and shrinking pools of prospective parents. It goes on to highlight the harmful effects of discriminatory, faith‐based placement and certification services on foster children; explains how such policies and practices breach the City's parens patriae duty to maximize the pool of prospective foster families for foster children; and presents data documenting negative outcomes for foster youth when placement options are circumscribed by categorical exclusion of LGBTQ+ families. The piece concludes with a critical examination of the Supreme Court's failure to factor children's best interests in its constitutional calculus and how the Court's holding endorses religious based action by government contractors that will harm vulnerable children confined to our nation's overcrowded foster care systems.