bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin rejuvenates Nap1l2‐impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming
Authors: Liu Fan , Han Ruohui , Nie Shaochen , Cao Yuxin , Zhang Xinming , Gao Feng , Wang Zhengyang , Xing Liangyu , Ouyang Zhaoguang , Sui Lei , Mi Wenyi , Wu Xudong , Sun Lu , Hu Meilin , Liu Dayong
Published: February 2024

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1‐like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE‐Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE‐Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l‐arginine and expression of inducible nitric oxide synthase in OE‐Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.
Capital controls, banking competition, and monetary policy
Authors: Ghossoub Edgar A. , Harrison Andre , Reed Robert R.
Published: February 2024

How do capital controls and banking concentration affect economic development? This paper develops a general equilibrium model to study these important issues. To do so, we construct a framework with heterogeneous agents and imperfectly competitive financial intermediaries who help depositors manage liquidity risk. Importantly, higher levels of concentration raise the cost of domestic borrowing which increase the reliance on international capital markets. Finally, once the rate of money growth is sufficiently high, capital controls bind and the effects of monetary policy on capital formation are more pronounced.
Spatial and molecular anatomy of the endometrium during embryo implantation: a current overview of key regulators of blastocyst invasion
Authors: Akaeda Shun , Aikawa Shizu , Hirota Yasushi
Published: February 2024

Embryo implantation is composed of three steps: blastocyst apposition, adhesion/attachment and invasion. Blastocyst invasion has been studied less extensively than the other two events. Historically, studies conducted using electron microscopy have shown the removal of epithelial cells in the vicinity of the attached blastocysts in rodents, although the underlying mechanisms have remained unclear. Here, we describe recent studies using mice with uterine‐specific gene deletion that demonstrated important roles for nuclear proteins such as progesterone receptor, hypoxia inducible factor and retinoblastoma in the regulation of embryo invasion. In these mouse models, the detachment of the endometrial luminal epithelium, decidualization in the stroma, and the activation of trophoblasts have been found to be important in ensuring embryo invasion. This review summarizes the molecular signaling associated with these cellular events, mainly evidenced by mouse models.
Mitochondrial dysfunction and cisplatin sensitivity in gastric cancer: GDF15 as a master player
Authors: Cavinato Maria
Published: February 2024

Gastric cancer, a major global health concern, poses challenges in effective treatment, notably due to chemoresistance. This study investigates the role of growth/differentiation factor‐15 (GDF‐15) in mitochondrial dysfunction and its impact on cisplatin sensitivity in gastric cancer cells. In this issue of The FEBS Journal, Wang et al. demonstrate that GDF15 upregulation is associated with cisplatin insensitivity, mediated by the ATF4‐CHOP pathway and reactive oxygen species‐activated general control nonderepressible 2 [Wang S‐F et al. (2023) FEBS J, https://doi.org/10.1111/febs.16992]. Connecting these insights, we explore the broader implications of GDF15 expression in the aging‐cancer axis, particularly its involvement in cellular senescence and the senescence‐associated secretory phenotype (SASP). This study suggests that GDF15 released by senescent cells could contribute to tumor progression, indicating potential avenues for therapeutic intervention by targeting senescent cells and their SASP. While the study provides valuable insights into mitigating cisplatin resistance, further research is crucial to fully understand the role of GDF15 in the tumor microenvironment and its potential feedback loops promoting tumorigenesis.
Kinetic simulation of convection drying for its effect on nutritional, functional, and phytochemical profiling of Colocasia antiquorum and Nasturtium officinale leaves of the Himalayan region
Authors: Phull Tanvi , Phian Pallavi , Gupta Mahesh
Published: February 2024

Colocasia antiquorum (Taro) and Nasturtium officinale (Watercress) leaves are highly potent indigenous crops with rich nutritional and phytochemical profiles. The leaves were mathematically modeled, using thin‐layer models, to study the process kinetics for convection drying and its cumulative effect on the physico‐chemical, nutritional, functional, phytochemical, and targeted metabolite profiles. The best‐fit model for C. antiquorum was the two‐term model, whereas for N. officinale, Page model showed the best adequacy with the determination of least Chi‐square and high co‐efficient along with root mean square error. The color and pigment degradation were the prominent changes observed in the quality characteristics of C. antiquorum and N. officinale leaves depicted by the color degradation study. The nutritional composition was significantly affected by the convective drying with reduced ash, protein, and phenolic contents. The extraction yields were however higher along with some elevated metabolite contents estimated for convection drying in comparison to freeze‐dried leaves.

Practical applications

This study explores the drying kinetic behavior for the progression of moisture loss occurring over the drying time and moderation of drying to achieve a desired moisture content at certain drying rates. The quality characterization before and after selected drying conditions revealed the sensitivity of the chlorophyll/carotenoid pigments, nutrients, and phenolics retained significantly after the end point of drying. Also, the effect of convective drying on the physicochemical, nutritional, and phytochemical contents was significant, which edifies the extent of alterations occurring due to convective drying on the quality characteristics of Colocasia antiquorum (Taro) and Nasturtium officinale (Watercress) leaves. Consequently, these two leafy vegetables hold good potential as crops to be promoted for nutritional security and health and wellness due to their rich bioactive profiles.
Malnutrition risk assessment using a machine learning‐based screening tool: A multicentre retrospective cohort
Authors: Parchure Prathamesh , Besculides Melanie , Zhan Serena , Cheng Fu‐yuan , Timsina Prem , Cheertirala Satya Narayana , Kersch Ilana , Wilson Sara , Freeman Robert , Reich David , Mazumdar Madhu , Kia Arash
Published: February 2024

Background

Malnutrition is associated with increased morbidity, mortality, and healthcare costs. Early detection is important for timely intervention. This paper assesses the ability of a machine learning screening tool (MUST‐Plus) implemented in registered dietitian (RD) workflow to identify malnourished patients early in the hospital stay and to improve the diagnosis and documentation rate of malnutrition.

Methods

This retrospective cohort study was conducted in a large, urban health system in New York City comprising six hospitals serving a diverse patient population. The study included all patients aged ≥ 18 years, who were not admitted for COVID‐19 and had a length of stay of ≤ 30 days.

Results

Of the 7736 hospitalisations that met the inclusion criteria, 1947 (25.2%) were identified as being malnourished by MUST‐Plus‐assisted RD evaluations. The lag between admission and diagnosis improved with MUST‐Plus implementation. The usability of the tool output by RDs exceeded 90%, showing good acceptance by users. When compared pre‐/post‐implementation, the rate of both diagnoses and documentation of malnutrition showed improvement.

Conclusion

MUST‐Plus, a machine learning‐based screening tool, shows great promise as a malnutrition screening tool for hospitalised patients when used in conjunction with adequate RD staffing and training about the tool. It performed well across multiple measures and settings. Other health systems can use their electronic health record data to develop, test and implement similar machine learning‐based processes to improve malnutrition screening and facilitate timely intervention.
Vegetarian diets and risk of nonalcoholic fatty liver disease: An observational study of National Health and Nutrition Examination Survey 2005–2018 using propensity score methods
Authors: Li Rui , Li Ming , Fly Alyce D. , Bidulescu Aurelian , Luo Juhua
Published: February 2024

Background

Studies on the association between vegetarian diets and nonalcoholic fatty liver disease (NAFLD) are limited and have inconsistent results. This study aims to explore the association between vegetarian diets and NAFLD and compare the stage of fibrosis between vegetarians and nonvegetarians in a US representative sample.

Methods

Cross‐sectional data from 23,130 participants aged ≥20 years were obtained from the National Health and Nutrition Examination Survey, 2005–2018. Vegetarian status was classified based on two 24‐h dietary recalls. We examined the association between vegetarian diets and the risk of NAFLD using the propensity score weighting method.

Results

Vegetarian diets were significantly associated with decreases in hepatic steatosis index (HSI), US fatty liver index and nonalcoholic fatty liver disease fibrosis score with mean differences of −2.70 (95% confidence interval [CI]: −3.69, −1.70), −3.03 (95% CI: −7.15, −0.91) and −0.12 (95% CI: −0.26, −0.01), respectively. While modelling the risk of NAFLD, we estimated that vegetarians were 53% less likely to have NAFLD assessed by HSI (odds ratios [OR]: 0.47; 95% CI: 0.34, 0.65). The effect of vegetarian diets was higher among individuals with lower waist circumferences (OR: 0.20) than among those with higher waist circumferences (OR: 0.53, = 0.004). However, the association was largely attenuated after adjusting for body mass index and diabetes status. No significant association was identified between vegetarian diets and advanced fibrosis.

Conclusions

Vegetarian diets were associated with a lower prevalence of NAFLD among US adults, and the association appeared to be stronger in people with lower waist circumferences. Further studies are warranted to replicate our findings.
Is multiple wavelength diode laser for facial contouring safe?
Authors: Yi Kyu‐Ho , Oh Wook , Kim Hyoung‐Moon , Park Hyun‐Jun
Published: February 2024

The multiple wavelength diode laser (MWDL) is a sophisticated device designed to target deeper skin layers by emitting various wavelengths. Its unique feature is the ability to deliver heat to specific depths within the tissue using different wavelengths while simultaneously cooling the skin surface. Recent research by Choi et al. suggests that wavelengths of 755 and 810 nm can induce carbonization in hair follicles, while the 1064 nm wavelength penetrates deeper into tissues. MWDL has been proposed for fat redistribution in aging, but concerns have been raised regarding ocular safety and potential tissue damage, particularly when used near the eyes. Studies have shown ocular injuries during cosmetic laser procedures, emphasizing the need for robust ocular protection and safety protocols. Additionally, there are reports of internal ischemic necrosis and burns, highlighting the importance of precise energy settings and parameter management. While MWDL shows promise, further research and comprehensive guidelines are needed to ensure safe and effective usage in clinical practice.
Proceed with caution: Standard protocol exercise stress tests fail to replicate the diagnostic utility of supine‐stand tests for long QT syndrome
Authors: Pinsky Alexa M. , Kulkarni Veda K. , Bos J. Martijn , Neves Raquel , Allison Thomas G. , Ackerman Michael J.
Published: February 2024

Background

Long QT syndrome (LQTS) is a sudden death predisposing condition characterized by ECG‐derived prolongation of the QT interval. Previous studies have demonstrated that the supine‐stand test may aid in the diagnosis of LQTS as patients fail to shorten their QT interval in response to standing up. The aim of this study was to evaluate the diagnostic accuracy of ECG data derived from standard protocol, clinically performed treadmill exercise stress tests (TESTs) in their ability to mimic the formal supine‐stand test.

Methods

We performed a retrospective review of 478 TESTs from patients evaluated for LQTS. Patients referred for evaluation of LQTS but who were dismissed as normal served as controls. Heart rate & QT values were obtained from standard protocol TESTs.

Results

Overall, 243 patients with LQTS (125 LQT1, 63 LQT2, 55 LQT3; 146 [60%] female, mean age at TEST 30 ± 17 years) and 235 controls (142 [60%] female, mean age 24 ± 15 years) were included. The paired ΔQTc (QTcStand‐QTcSupine) was similar between LQTS (−5 ± 26) and controls (−2 ± 25; p = .2). During position change, the QT interval shortened by ≥20 ms in 33% of LQTS patients, remained unchanged in 62%, and increased in 5% of LQTS patients which was similar to controls (shortened in 40%, unchanged in 54%, and increased in 6% of controls; p = .2). Receiver‐operator curve analysis to test the diagnostic ability of supine‐stand ΔQT performed poorly in differentiating LQTS from controls with an of AUC 0.52 (p = .4).

Conclusion

TESTs should be used with caution when trying to interpret supine‐stand changes for diagnosis of LQTS.
Cannon A wave validation as a diagnostic tool in paroxysmal supraventricular tachycardias
Authors: González‐Casal David , Pérez‐Castellanos Alberto , Flores Nina Soto , Carta‐Bergaz Alejandro , González‐Torrecilla Esteban , Bruña Fernández Vanesa , Ávila Pablo , Atienza Felipe , Arenal Ángel , González‐Panizo Jorge , Fernández‐Avilés Francisco , Cabrera José Angel , Datino Tomás
Published: February 2024

Objective

The presence of cannon A waves, the so called “frog sign”, has traditionally been considered diagnostic of atrioventricular nodal re‐entrant tachycardia (AVNRT). Nevertheless, it has never been systematically evaluated. The aim of this study is to assess the independent diagnostic utility of cannon A waves in the differential diagnosis of supraventricular tachycardias (SVTs).

Methods

We prospectively included 100 patients who underwent an electrophysiology (EP) study for SVT. The right jugular venous pulse was recorded during the study. In 61 patients, invasive central venous pressure (CVP) was registered as well. CVP increase is thought to be related with the timing between atria and ventricle depolarization; two groups were prespecified, the short VA interval tachycardias (including typical AVNRT and atrioventricular reciprocating tachycardia (AVRT) mediated by a septal accessory pathway) and the long VA interval tachycardias (including atypical AVNRT and AVRT mediated by a left free wall accessory pathway).

Results

The relationship between cannon A waves and AVNRT did not reach the statistical significance (OR: 3.01; p = .058); On the other hand, it was clearly associated with the final diagnosis of a short VA interval tachycardia (OR: 10.21; p < .001). CVP increase showed an inversely proportional relationship with the VA interval during tachycardia (b = −.020; p < .001). CVP increase was larger in cases of AVNRT (4.0 mmHg vs. 1.2 mmHg; p < .001) and short VA interval tachycardias (3.9 mmHg vs. 1.2 mmHg; p < .001).

Conclusion

The presence of cannon A waves is associated with the final diagnosis of short VA interval tachycardias.
The impacts of rising vapour pressure deficit in natural and managed ecosystems
Authors: Novick Kimberly A. , Ficklin Darren L. , Grossiord Charlotte , Konings Alexandra G. , Martínez‐Vilalta Jordi , Sadok Walid , Trugman Anna T. , Williams A. Park , Wright Alexandra J. , Abatzoglou John T. , Dannenberg Matthew P. , Gentine Pierre , Guan Kaiyu , Johnston Miriam R. , Lowman Lauren E. L. , Moore David J. P. , McDowell Nate G.
Published: February 2024

An exponential rise in the atmospheric vapour pressure deficit (VPD) is among the most consequential impacts of climate change in terrestrial ecosystems. Rising VPD has negative and cascading effects on nearly all aspects of plant function including photosynthesis, water status, growth and survival. These responses are exacerbated by land–atmosphere interactions that couple VPD to soil water and govern the evolution of drought, affecting a range of ecosystem services including carbon uptake, biodiversity, the provisioning of water resources and crop yields. However, despite the global nature of this phenomenon, research on how to incorporate these impacts into resilient management regimes is largely in its infancy, due in part to the entanglement of VPD trends with those of other co‐evolving climate drivers. Here, we review the mechanistic bases of VPD impacts at a range of spatial scales, paying particular attention to the independent and interactive influence of VPD in the context of other environmental changes. We then evaluate the consequences of these impacts within key management contexts, including water resources, croplands, wildfire risk mitigation and management of natural grasslands and forests. We conclude with recommendations describing how management regimes could be altered to mitigate the otherwise highly deleterious consequences of rising VPD.
Blue light impairs the repair of UVB‐induced pyrimidine dimers in a human skin model
Authors: Douki Thierry , Bacqueville Daniel , Jacques Carine , Geniès Camille , Roullet Nicolas , Bessou‐Touya Sandrine , Duplan Hélène
Published: February 2024

In recent years, interest is growing in the biological cutaneous effects of high‐energy visible light (400–450 nm). In the present study, we explored the impact of blue light (BL) on the repair of pyrimidine dimers, the major class of premutagenic DNA damage induced by exposure to sunlight. We unambiguously demonstrate that the exposure of in vitro reconstructed human epidermis to environmentally relevant doses of BL strongly decreases the rate of repair of cyclobutane pyrimidine dimers and pyrimidine (6‐4) pyrimidone photoproducts induced by a subsequent UVB irradiation. Using the highly sensitive and specific liquid chromatography‐tandem mass spectrometry assay, we did not observe induction of pyrimidine dimers by BL alone. Finally, we showed that application, during the BL exposure step, of a formula containing a new filter, named TriAsorB and affording BL photoprotection, prevented the decrease in DNA repair efficiency. These results emphasize the potential deleterious effects of BL on DNA repair and the interest in providing adequate skin protection against this wavelength range of sunlight.
Impact of individual, combined and sequential stress on photosynthesis machinery in rice (Oryza sativa L)
Authors: Anwar Khalid , Joshi Rohit , Bahuguna Rajeev N. , Govindjee Govindjee , Sasidharan Rashmi , Singla‐Pareek Sneh L. , Pareek Ashwani
Published: February 2024

Abiotic stresses such as heat, drought and submergence are major threats to global food security. Despite simultaneous or sequential occurrence of these stresses being recurrent under field conditions, crop response to such stress combinations is poorly understood. Rice is a staple food crop for the majority of human beings. Exploitation of existing genetic diversity in rice for combined and/or sequential stress is a useful approach for developing climate‐resilient cultivars. We phenotyped ~400 rice accessions under high temperature, drought, or submergence and their combinations. A cumulative performance index revealed Lomello as the best performer across stress and stress combinations at the seedling stage. Lomello showed a remarkable ability to maintain a higher quantum yield of photosystem (PS) II photochemistry. Moreover, the structural integrity of the photosystems, electron flow through both PSI and PSII and the ability to protect photosystems against photoinhibition were identified as the key traits of Lomello across the stress environments. A higher membrane stability and an increased amount of leaf chlorophyll under stress may be due to an efficient management of reactive oxygen species (ROS) at the cellular level. Further, an efficient electron flow through the photosystems and, thus, a higher photosynthetic rate in Lomello is expected to act as a sink for ROS by reducing the rate of electron transport to the high amount of molecular oxygen present in the chloroplast. However, further studies are needed to identify the molecular mechanism(s) involved in the stability of photosynthetic machinery and stress management in Lomello during stress conditions.
Exploring the exponential sensitivity of risk perception in the COVID‐19 pandemic
Authors: Kim Min‐Kyu , Lee Bo‐Eun , Chung Ji‐Bum
Published: February 2024

Individual's risk perception regarding specific hazards is a dynamic process that evolves over time. This study analyzed the relationship between the number of COVID‐19 cases and the South Korean public's risk perceptions from the outset of the pandemic to the recent past. More than 70 repeated cross‐sectional surveys were conducted biweekly to measure individuals’ risk perception. An autoregressive integrated moving average with explanatory variable time series analysis was used to characterize the relationship between the number of COVID‐19 cases and level of risk perceptions. It revealed that individuals’ risk perception and the number of COVID‐19 cases were not linearly related but were logarithmically correlated. This finding can be understood as a psychic numbing effect, suggesting that people's perception of risk is not linear but rather exponentially sensitive to changes. The findings also revealed a significant influence of individuals’ trust in local governments on their risk perceptions, highlighting the substantial role played by local governments in direct risk management during the COVID‐19 pandemic.
Powered versus manual toothbrushes for plaque removal and gingival health amongst 55 and older individuals: A systematic review and meta‐analysis
Authors: Saroya Komal Kaur , Gupta Arpit , Shrivastava Richa , Mehta Nishant , Goyal Ashima
Published: February 2024

Objective

To compare manual and powered toothbrushes in older adults and to culminate available clinical evidence concerning efficiency with respect to plaque removal and reduced gingivitis.

Background

Manual dexterity decreases with age, negatively impacting daily activities, including oral hygiene practices. Effective plaque control in this age group is directly related to nutrition and overall health. Therefore, developing oral health interventions tailored to the ageing population is essential.

Material and methods

This systematic review was registered with PROSPERO (Registration No. CRD42023415876). Five electronic databases were searched to identify randomized controlled trials published from inception until March 2023. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analyses were also performed for gingival, plaque, and bleeding indices.

Results

A total of 2118 records were identified, and six eligible publications were retrieved. Comparison of Plaque Indices between powered and manual toothbrushes showed a Standard mean difference (SMD) of −0.10; 95% CI [−0.37, 0.18] (p = .38). Comparison of the gingival index and bleeding index between powered and manual toothbrushes showed an SMD of −0.28; 95% CI [−0.72, 0.16] (p = .22) and SMD of −0.03 [−0.38, 0.32] (p = .84), respectively.

Conclusion

According to the available literature, this study suggests the need for more streamlined research to support the superiority of either powered or manual toothbrushes in improving oral health (as measured by the indices) among the older population. The results will hence have significant reverberations for older adults looking to improve their oral hygiene practices.
Spinal lymphoma in a goat
Authors: Nankemann Jannis , Holland Merrilee , Glamann Samantha , Cole Robert , Stockler Jenna , Moon Rachel
Published: February 2024

A 3‐year‐old Pygmy Wether was presented for chronic hindlimb paralysis. A neurological exam revealed nonambulatory paraplegia with absent deep pain nociception, lack of hindlimb withdrawal reflexes, and paraspinal pain on palpation with T3 to L3 neurolocalization. MRI of the lumbar spine revealed an extensive, dorsal to dorsolateral, severely compressive, heterogeneously contrast‐enhancing extradural lesion of the lumbar spine with intervertebral foraminal extension into the surrounding paraspinal musculature. Vertebral bone marrow involvement was also noted in the L5 and L6 vertebrae. A diagnosis of lymphoma was obtained after cytological sampling. This is the first case report describing specific MRI findings (signal characteristics, enhancement pattern, and perilesional changes) in a goat with paraspinal lymphoma.
Boundedness of the base varieties of certain fibrations
Authors: Li Zhan
Published: February 2024

It is conjectured that the base varieties of the Iitaka fibrations are bounded when the Iitaka volumes are bounded above. We confirm this conjecture for Iitaka ‐lc Fano type fibrations.
The Loewner–Kufarev energy and foliations by Weil–Petersson quasicircles
Authors: Viklund Fredrik , Wang Yilin
Published: February 2024

We study foliations by chord–arc Jordan curves of the twice punctured Riemann sphere using the Loewner–Kufarev equation. We associate to such a foliation a function on the plane that describes the “local winding” along each leaf. Our main theorem is that this function has finite Dirichlet energy if and only if the Loewner driving measure has finite Loewner–Kufarev energy, defined by
whenever is of the form , and set to otherwise. Moreover, if either of these two energies is finite, they are equal up to a constant factor, and in this case, the foliation leaves are Weil–Petersson quasicircles. This duality between energies has several consequences. The first is that the Loewner–Kufarev energy is reversible, that is, invariant under inversion and time reversal of the foliation. Furthermore, the Loewner energy of a Jordan curve can be expressed using the minimal Loewner–Kufarev energy of those measures that generate the curve as a leaf. This provides a new and quantitative characterization of Weil–Petersson quasicircles. Finally, we consider conformal distortion of the foliation and show that the Loewner–Kufarev energy satisfies an exact transformation law involving the Schwarzian derivative. The proof of our main theorem uses an isometry between the Dirichlet energy space on the unit disc and that we construct using Hadamard's variational formula expressed by means of the Loewner–Kufarev equation. Our results are related to ‐parameter duality and large deviations of Schramm–Loewner evolutions coupled with Gaussian random fields.
Anomalous reflection from a two-layered marine sediment
Authors: Buckingham Michael J.
Published: February 2024

This paper concerns the theory of acoustic reflection from a two-layered marine sediment, the upper layer of which consists of a fine-grained material (mud). The seawater above and basement below the layer are treated as homogeneous half-spaces. Within the mud layer, the density is taken to be constant, and three sound speed profiles are considered: uniform, linear, and inverse-square. The reflection coefficient exhibits a background component that is similar in all three cases, exhibiting only a weak sensitivity to the gradient of the profile, the frequency, and the depth of the layer. Additionally, the two profiles with a non-zero gradient, linear and inverse-square, exhibit a sequence across grazing angle of narrow spikes of total reflection. The angular distribution of this acoustic glint is highly sensitive to the frequency and depth of the layer, and mildly so to the gradient. As the gradient approaches zero, the glint vanishes and the reflection coefficient reduces identically to the form of a uniform sound speed profile. If it were detectable, the angular distribution of the glint, observed at several frequencies, could constitute a unique, sensitive set of “fingerprints,” allowing the depth and sound speed gradient of the mud layer to be inferred.
Effects of Blood Flow Restriction on Balance Performance During Dynamic Balance Exercises in Individuals With Chronic Ankle Instability
Authors: Clark Krista , Trickett Justin , Donovan Luke , Dawson Jordan , Goetschius John
Published: February 2024

Context: Blood flow restriction (BFR) is a rehabilitation tool which may introduce a constraint, similar to muscle fatigue, that challenge patients’ sensorimotor system during balance exercises. The purpose of our study was to examine whether adding BFR to dynamic balance exercises produced a decrease in balance performance and an increase in ratings of perceived exertion and instability in individuals with chronic ankle instability (CAI) compared with dynamic balance exercises without BFR. Designs: Crossover design. Methods: Our sample included N = 25 young adults with a history of CAI. Participants completed 2 laboratory visits. At each visit, participants completed 4 sets (30×-15×-15×-15×) of dynamic balance exercises, performed similar to the modified star excursion balance test (SEBT), once with BFR and once with control (no BFR) conditions. We measured composite SEBT scores at baseline and during the final repetitions of each set of balance exercise (sets 1–4). We also measured ratings of perceived exertion and instability following each balance exercise set. Results: We observed no difference in composite SEBT scores between conditions at baseline; however, composite SEBT scores were significantly lower during all balance exercises sets 1 to 4 with the BFR condition compared with control. During the BFR condition, composite SEBT scores were significantly lower during all balance exercise sets compared with baseline. During the control condition, composite SEBT scores did not significantly change between baseline and each balance exercise set. Ratings of perceived exertion and instability scores were significantly greater in the BFR group compared with the control group during all balance exercise sets. Conclusions: Individuals with CAI demonstrated lower composite SEBT scores and greater perceived instability and exertion during dynamic balance exercise with BFR compared to without BFR. BFR introduced a novel muscle fatigue constraint during dynamic balance exercises in individuals with CAI. Additional research is needed to determine if adding BFR to balance training could improve clinical outcomes in CAI patients.
Mechanisms of biased agonism by Gα
i/o
-biased stapled peptide agonists of the relaxin-3 receptor
Authors: Jayakody Tharindunee , Inoue Asuka , Kannan Srinivasaraghavan , Nakamura Gaku , Kawakami Kouki , Mendis Krishan , Nguyen Thanh-Binh , Li Jianguo , Herr Deron R. , Verma Chandra S. , Dawe Gavin S.
Published: February 2024

The neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gα
i/o
-biased agonists of RXFP3. These peptides did not induce recruitment of β-arrestin1/2 to RXFP3 by GPCR kinases (GRKs), in contrast to relaxin-3, which enabled the GRK2/3-mediated recruitment of β-arrestin1/2 to RXFP3. Relaxin-3 and the previously reported peptide 4 (an i, i+4 stapled relaxin-3 B chain) did not exhibit biased signaling. The staple linker of peptide 4 and parts of both the A chain and B chain of relaxin-3 interacted with extracellular loop 3 (ECL3) of RXFP3, moving it away from the binding pocket, suggesting that unbiased ligands promote a more open conformation of RXFP3. These findings highlight roles for the A chain and the N-terminal residues of the B chain of relaxin-3 in inducing conformational changes in RXFP3, which will help in designing selective biased ligands with improved therapeutic efficacy.
RNAs create a sticky situation
Authors: Wong Wei
Published: February 2024

Glycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.
Effect of the aggregated protein dye YAT2150 on
Leishmania
parasite viability
Authors: Román-Álamo Lucía , Avalos-Padilla Yunuen , Bouzón-Arnáiz Inés , Iglesias Valentín , Fernández-Lajo Jorge , Monteiro Juan M. , Rivas Luis , Fisa Roser , Riera Cristina , Andreu David , Pintado-Grima Carlos , Ventura Salvador , Arce Elsa M. , Muñoz-Torrero Diego , Fernàndez-Busquets Xavier
Published: February 2024

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC
50
) of approximately 0.5 µM against promastigote and amastigote stages of
Leishmania infantum
. The encapsulation in liposomes of YAT2150 significantly improved its
in vitro
IC
50
to 0.37 and 0.19 µM in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 µM. YAT2150 became strongly fluorescent when binding intracellular protein deposits in
Leishmania
cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite
Plasmodium falciparum
, the inhibition of protein aggregation. In
Leishmania major
, YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both
Plasmodium
and
Leishmania
, thus being a potential drug for the treatment of co-infections of both parasites.
Successional changes in bacterial phyllosphere communities are plant-host species dependent
Authors: Bechtold Emily K. , Wanek Wolfgang , Nuesslein Benedikt , DaCosta Michelle , Nüsslein Klaus
Published: February 2024

Leaf surface microbiomes have the potential to influence agricultural and ecosystem productivity. We assessed their stability by determining composition, functional resistance, and resilience. Resistance is the degree to which communities remain unchanged as a result of disturbance, and resilience is the ability of a community to recover to pre-disturbance conditions. By understanding the mechanisms of community assembly and how they relate to the resistance and resilience of microbial communities under common environmental stresses such as drought, we can better understand how communities will adapt to a changing environment and how we can promote healthy agricultural microbiomes. In this study, phyllosphere compositional stability was highly related to plant host species phylogeny and, to a lesser extent, known stress tolerances. Phyllosphere community assembly and stability are a result of complex interactions of ecological processes that are differentially imposed by host species.
Anthropogenic contamination sources drive differences in antimicrobial-resistant
Escherichia coli
in three urban lakes
Authors: Wight Jordan , Byrne Alexander S. , Tahlan Kapil , Lang Andrew S.
Published: February 2024

A One Health perspective is crucial to understand the extent of antimicrobial resistance (AMR) globally, and investigation of AMR in the environment has been increasing in recent years. However, most studies have focused on waterways that are directly polluted by sewage, industrial manufacturing, or agricultural activities. Therefore, there remains a lack of knowledge about more natural, less overtly impacted environments. Through phenotypic and genotypic investigation of AMR in
Escherichia coli
, this study adds to our understanding of the extent and patterns of resistance in these types of environments, including over a time series, and showed that complex biotic and abiotic factors contribute to the patterns observed. Our study further emphasizes the importance of incorporating the surveillance of microbes in freshwater environments in order to better comprehend potential risks for both human and animal health and how the environment may serve as a sentinel for potential future clinical infections.
Rhodococcus
infection: a 10-year retrospective analysis of clinical experience and antimicrobial susceptibility profile
Authors: Ranganath Nischal , Mendoza Maria Alejandra , Stevens Ryan , Kind Dalton , Wengenack Nancy , Shah Aditya
Published: February 2024

Rhodococcus equi
is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-
equi Rhodococcus
spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of
Rhodococcus
infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of
Rhodococcus
infections between June 2012 and 2022 at our tertiary academic medical center. Identification of
Rhodococcus
spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of
Rhodococcus
spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources.
R. equi/hoagii, R. corynebacterioides
, and
R. erythropolis
were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-
equi
species showed a significantly more favorable AST profile relative to
R. equi
. Clinically significant
Rhodococcus
infection was rare with 10 cases diagnosed (majority due to
R. equi
) and managed. The majority of patients received 2- or 3-drug combination therapy for 2–6 months, with favorable clinical response. Significant differences in AST were observed between
R. equi
and non-
equi
species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for
R. equi
. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.
NS1-mediated enhancement of MVC transcription and replication promoted by KAT5/H4K12ac
Authors: Zhang Xueyan , Guo Jianhui , Xu Huanzhou , Ding Shuang , Liu Lishi , Chen Zhen , Yang Jingwen , Liu Yi , Hao Haojie , Huang Fang , Qiu Jianming , Guan Wuxiang , Sun Yuning , Liu Haibin
Published: February 2024

Histone modifications function in both cellular and viral gene expression. However, the roles of acetyltransferases and histone acetylation in parvoviral infection remain poorly understood. In the current study, we found the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), promoted the replication and transcription of parvovirus minute virus of canines (MVC). Notably, the expression of host acetyltransferases KAT5, GTF3C4, and KAT2A was increased in MVC infection, as well as H4 acetylation (H4K12ac). KAT5 is not only responsible for H4K12ac but also crucial for viral replication and transcription. The viral nonstructural protein NS1 interacted with KAT5 and enhanced its expression. Further study showed that Y44 in KAT5, which may be tyrosine-phosphorylated, is indispensable for NS1-mediated enhancement of KAT5 and efficient MVC replication. The data demonstrated that NS1 interacted with KAT5, which resulted in an enhanced H4K12ac level to promote viral replication and transcription, implying the epigenetic addition of H4K12ac in viral chromatin-like structure by KAT5 is vital for MVC replication.

IMPORTANCE

Parvoviral genomes are chromatinized with host histones. Therefore, histone acetylation and related acetyltransferases are required for the virus to modify histones and open densely packed chromatin structures. This study illustrated that histone acetylation status is important for MVC replication and transcription and revealed a novel mechanism that the viral nonstructural protein NS1 hijacks the host acetyltransferase KAT5 to enhance histone acetylation of H4K12ac, which relies on a potential tyrosine phosphorylation site, Y44 in KAT5. Other parvoviruses share a similar genome organization and coding potential and may adapt a similar strategy for efficient viral replication and transcription.
Characterization of
Acinetobacter baumannii
core oligosaccharide synthesis reveals novel aspects of lipooligosaccharide assembly
Authors: VanOtterloo Leah M. , Macias Luis A. , Powers Matthew J. , Brodbelt Jennifer S. , Trent M. Stephen
Published: February 2024

A fundamental feature of Gram-negative bacteria is their outer membrane that protects the cell against environmental stressors. This defense is predominantly due to its asymmetry, with glycerophospholipids located in the inner leaflet and lipopolysaccharide (LPS) or lipooligosaccharide (LOS) confined to the outer leaflet. LPS consists of a lipid A anchor, a core oligosaccharide, and a distal O-antigen while LOS lacks O-antigen. While LPS/LOS is typically essential for growth, this is not the case for
Acinetobacter baumannii
. Despite this unique property, the synthesis of the core oligosaccharide of
A. baumannii
LOS is not well-described. Here, we characterized the LOS chemotypes of
A. baumannii
strains with mutations in a predicted core oligosaccharide locus via tandem mass spectrometry. This allowed for an extensive identification of genes required for core assembly that can be exploited to generate precise structural LOS modifications in many
A. baumannii
strains. We further investigated two chemotypically identical yet phenotypically distinct mutants, ∆
2903
and ∆
lpsB
, that exposed a possible link between LOS and the peptidoglycan cell wall—two cell envelope components whose coordination has not yet been described in
A. baumannii
. Selective reconstruction of the core oligosaccharide via expression of 2903 and LpsB revealed that these proteins rely on each other for the unusual tandem transfer of two residues, KdoIII and N-acetylglucosaminuronic acid. The data presented not only allow for better usage of
A. baumannii
as a tool to study outer membrane integrity but also provide further evidence for a novel mechanism of core oligosaccharide assembly.

IMPORTANCE

Acinetobacter baumannii
is a multidrug-resistant pathogen that produces lipooligosaccharide (LOS), a glycolipid that confers protective asymmetry to the bacterial outer membrane. The core oligosaccharide is a ubiquitous component of LOS that typically follows a well-established model of synthesis. In addition to providing an extensive analysis of the genes involved in the synthesis of the core region, we demonstrate that this organism has evidently diverged from the long-held archetype of core synthesis. Moreover, our data suggest that
A. baumannii
LOS assembly is important for cell division and likely intersects with the synthesis of the peptidoglycan cell wall, another essential component of the Gram-negative cell envelope. This connection between LOS and cell wall synthesis provides an intriguing foundation for a unique method of outer membrane biogenesis and cell envelope coordination.
Botulinum neurotoxin X lacks potency in mice and in human neurons
Authors: Gregg Brieana M. , Matsumura Takuhiro , Wentz Travis G. , Tepp William H. , Bradshaw Marite , Stenmark Pål , Johnson Eric A. , Fujinaga Yukako , Pellett Sabine
Published: February 2024

Botulinum neurotoxins (BoNTs) are a class of toxins produced by
Clostridium botulinum
(
C. botulinum
) and other species of
Clostridia
. BoNT/X is a putative novel botulinum neurotoxin identified through genome sequencing and capable of SNARE cleavage, but its neurotoxic potential in humans and vertebrates remained unclear. The
C. botulinum
strain producing BoNT/X, Strain 111, encodes both a plasmid-borne
bont/b2
as well as the chromosomal putative
bont/x
. This study utilized
C. botulinum
Strain 111 from Japan as well as recombinantly produced full-length BoNT/X to more fully analyze this putative pathogenic toxin. We confirmed production of full-length, catalytically active native BoNT/X by
C. botulinum
Strain 111, produced as a disulfide-bonded dichain polypeptide similar to other BoNTs. Both the purified native and the recombinant BoNT/X had high enzymatic activity
in vitro
but displayed very low potency in human-induced pluripotent stem cell-derived neuronal cells and in mice. Intraperitoneal injection of up to 50 µg of native BoNT/X in mice did not result in botulism; however, mild local paralysis was observed after injection of 2 μg into the gastrocnemius muscle. We further demonstrate that the lack of toxicity by BoNT/X is due to inefficient neuronal cell association and entry, which can be rescued by replacing the receptor binding domain of BoNT/X with that of BoNT/A. These data demonstrate that BoNT/X is not a potent vertebrate neurotoxin like the classical seven serotypes of BoNTs.

IMPORTANCE

The family of botulinum neurotoxins comprises the most potent toxins known to humankind. New members of this family of protein toxins as well as more distantly related homologs are being identified. The discovery of BoNT/X via bioinformatic screen in 2017 as a putative new BoNT serotype raised concern about its potential as a pathogenic agent with no available countermeasures. This study for the first time assessed both recombinantly produced and native purified BoNT/X for its vertebrate neurotoxicity.