bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonalcoholic fatty liver disease and female sexual dysfunction in Egyptian premenopausal women: is there a link between metabolic syndrome and sexual function?
Authors: Fouad Tamer Refaat , Mohamad Noha Ezzat , Elabd Mona , Abd-Elwahab Rokia , Elsary Asmaa Youness , Abd-Elghafar Tamer Samir , Elshimi Esam , Attia Ahmed
Published: July 2024

Background

Nonalcoholic fatty liver disease (NAFLD) is a major health problem with a paucity of available information about its impact on female sexual dysfunction (FSD).

Aim

We aimed to study the association between NAFLD and FSD in Egyptian premenopausal women.

Methods

Sexually active married premenopausal women who visited our NAFLD outpatient screening clinic (2019 to 2022) were divided into NAFLD and non-NAFLD (control) groups based on liver ultrasound and fatty liver index data. All participants completed the Arabic Female Sexual Function Index (ArFSFI) questionnaire. The resulting data were used to calculate the domains and total scores. FSD is then graded as follows: no FSD (≥28.2), minimal (21.7-28.1), mild (14.5-21.6), moderate (7.3-14.4), and severe (≤7.2).

Outcomes

We determined the proportions of patients and controls for whom ArFSFI scores indicated dissatisfaction with their sexual lives.

Results

Of 995 women participants whose FSFI scores were available, NAFLD was detected in 487 (48.9%) and absent in 508 (51.1%). The two groups were comparable in age, socioeconomic level, residence, and history of female genital cutting. The NAFLD patients had significantly much lower mean scores for the sexual arousal, lubrication, orgasm, satisfaction, and pain domains of the FSFI (P < .001 for all), while no statistical difference was noticed in the desire domain for NAFLD patients compared with the controls. NAFLD women had significantly lower mean total FSFI scores than the controls (mean [SD] 16.7 [6.8] vs 21.7 [5.1], respectively; P < .001) with higher rates of FSD (98.5% vs 82.1%; P < .001, respectively). Most NAFLD women had higher FSD grades than controls (%): no FSD (1.5, 17.9), minimal (20.6, 51.8), mild (42.5, 38.8), moderate (26.2, 9.4), and severe (10.7, none), respectively.

Clinical Implications

Given the high prevalence of FSD in patients with NAFLD, greater attention to FSF could improve the quality of life in patients with NAFLD.

Strengths and Limitations

This study was limited by the lack of testing of sex hormones and some other important factors that were not tested (eg, age, socioeconomic level, residence, and female genital cutting), as these characteristics were previously matched. Strengths of the study include the large study size, to our knowledge the largest to date to investigate the possible link between FSD and NAFLD in premenopausal women, together with the inclusion of the detailed version of the validated ArFSFI.

Conclusions

In Egyptian premenopausal women, NAFLD could harm their sexual function.
The difficult path to coalescence: massive black hole dynamics in merging low-mass dark matter haloes and galaxies
Authors: Partmann Christian , Naab Thorsten , Rantala Antti , Genina Anna , Mannerkoski Matias , Johansson Peter H
Published: July 2024

We present a high-resolution numerical study of the sinking and merging of massive black holes (MBHs) with masses in the range of $10^3 - 10^7 \, \mathrm{M}_\odot$ in multiple minor mergers of low-mass dark matter haloes without and with galaxies ($4\times 10^8 \, \mathrm{M}_\odot \lesssim {M}_{\mathrm{halo}} \lesssim 2\times 10^{10} \, \mathrm{M}_\odot)$. The ketju simulation code, a combination of the gadget tree solver with accurate regularized integration, uses unsoftened forces between the star/dark matter components and the MBHs for an accurate treatment of dynamical friction and scattering of dark matter/stars by MBH binaries or multiples. Post-Newtonian corrections up to order 3.5 for MBH interactions allow for coalescence by gravitational wave emission and gravitational recoil kicks. Low-mass MBHs ($\lesssim 10^5 \, \mathrm{M}_\odot$) hardly sink to the centre or merge. Sinking MBHs have various complex evolution paths – binaries, triplets, free-floating MBHs, and dynamically or recoil ejected MBHs. Collisional interactions with dark matter alone can drive MBHs to coalescence. The highest mass MBHs of $\gtrsim 10^6 \, \rm M_\odot$ mostly sink to the centre and trigger the scouring of dark matter and stellar cores. The scouring can transform a centrally baryon-dominated system into a dark-matter-dominated system. Our idealized high-resolution study highlights the difficulty to bring in and keep low-mass MBHs in the centres of low-mass haloes/galaxies – a remaining challenge for merger assisted MBH seed growth mechanisms.
An impulsive geomagnetic effect from an early-impulsive flare
Authors: Hudson Hugh S , Cliver Edward W , Fletcher Lyndsay , Diver Declan A , Gallagher Peter T , Li Ying , Osborne Christopher M J , Stark Craig , Su Yang
Published: July 2024

The geomagnetic ‘solar flare effect’ (SFE) results from excess ionization in the Earth’s ionosphere, famously first detected at the time of the Carrington flare in 1859. This indirect detection of a flare constituted one of the first cases of ‘multimessenger astronomy’, whereby solar ionizing radiation stimulates ionospheric currents. Well-observed SFEs have few-minute time-scales and perturbations of >10 nT, with the greatest events reaching above 100 nT. In previously reported cases, the SFE time profiles tend to resemble those of solar soft X-ray emission, which ionizes the D-region; there is also a less-well-studied contribution from Lyman α. We report here a specific case, from flare SOL2024-03-10 (M7.4), in which an impulsive SFE deviated from this pattern. This flare contained an ‘early impulsive’ component of exceptionally hard radiation, extending up to γ-ray energies above 1 MeV, distinctly before the bulk of the flare soft X-ray emission. We can characterize the spectral distribution of this early-impulsive component in detail, thanks to the modern extensive wavelength coverage. A more typical gradual SFE occurred during the flare’s main phase. We suggest that events of this type warrant exploration of the solar physics in the ‘impulse response’ limit of very short time-scales.
Effects of Recent Prior Dengue Infection on Risk and Severity of Subsequent SARS-CoV-2 Infection: A Retrospective Cohort Study
Authors: Tang Nicole , Lim Jue Tao , Dickens Borame , Chiew Calvin , Ng Lee Ching , Chia Po Ying , Leo Yee Sin , Lye David Chien , Tan Kelvin Bryan , Wee Liang En
Published: July 2024

Background and Aims

Elucidating whether prior dengue potentially confers cross-protection against COVID-19 is of public health importance in tropical countries at risk of overlapping dengue and COVID-19 epidemics. However, studies to date have yielded conflicting results. We aimed to assess effects of recent prior dengue infection on risk and severity of subsequent SARS-CoV-2 infection among adult Singaporeans.

Methods

A retrospective cohort study including all adult Singaporeans aged ≥18 years was conducted from 1 July 2021 through 31 October 2022, when a dengue outbreak driven by the DENV3 serotype preceded subsequent waves of SARS-CoV-2 Delta/Omicron transmission in Singapore. SARS-CoV-2 and dengue infection status were classified using national registries. Cox regression models adjusted for demographics, COVID-19 vaccination status, comorbidity, and socioeconomic-status were used to assess risks and severity (hospitalization, severe illness) of SARS-CoV-2 infection occurring after previous recorded dengue infection.

Results

A total of 3 366 399 individuals were included, contributing 1 399 696 530 person-days of observation. A total of 13 434 dengue infections and 1 253 520 subsequent SARS-CoV-2 infections were recorded; with an average of 94.7 days (standard deviation = 83.8) between dengue infection and SARS-CoV-2 infection. Preceding dengue infection was associated with a modest increase in risk of subsequent SARS-CoV-2 infection (adjusted hazards ratio [aHR] = 1.13; 95% confidence interval [CI], 1.08–1.17), and significantly elevated risk of subsequent COVID-19 hospitalization (aHR = 3.25; 95% CI, 2.78–3.82) and severe COVID-19 (aHR = 3.39; 95% CI, 2.29–5.03).

Conclusions

Increased risk of SARS-CoV-2 infection and adverse COVID-19 outcomes were observed following preceding dengue infection in a national population-based cohort of adult Singaporeans. This observation is of significance in tropical countries with overlapping dengue and COVID-19 outbreaks.
Single and Combined Serum Proteins Expressed in TB Infection are Candidates for Point-of-care Diagnostic Testing of Active TB Patients in Lambaréné, Gabon
Authors: Essone Paulin N , Lotola-Mougeni Fabrice , Adegbite Bayode R , Kokou Kossiwa , Otogo N'Nang E , Mabicka Eddy , Alabi Ayodele , Djoba Siawaya Joel F , Kremsner Peter G , Grobusch Martin P , Agnandji Selidji T
Published: July 2024

Background and Objectives

Point-of-care testing using nonsputum samples like serum or plasma proteins can improve tuberculosis (TB) patients access to a definitive diagnosis, especially in resource-constrained and remote areas. Recently, approximately 400 proteins were identified as playing a role in the pathogenesis of TB, offering a translational clinical research repository for TB. In a previous manuscript, we proved the potential use of these proteins for point-of-care testing for active TB diagnosis. The present work aims to confirm the performance of single and combination proteins to select the best candidate biomarkers for further development as a diagnostic testing tool for active TB.

Methods

Seventy-four participants were assessed on the diagnostic performance of 17 single proteins and combinations of 2 to 4 proteins to diagnose active TB. The selection criteria included differential expression of the proteins between active TB and community-acquired pneumonia (CAP) and a performance rate ≥70% for active TB.

Results

SULT4A1, WASPF3, SPTLC1, FAM107B, SORCS2, and CYTOb561 were differentially expressed in TB compared to CAP patients. Two single proteins, SULT4A1 and WASPF3, performed ≥70% to discriminate active TB from CAP patients. The diagnostic performance of 3 protein-based combinations of active TB was 81% after leave-one-out cross-validation.

Conclusion

Single proteins and 3 protein-based combinations are candidate biomarkers for diagnosing active TB disease. A large and prospective study will confirm their performance as complementary diagnostic tools to rapid diagnostic methods for detecting active TB.
Artemisinin-induced cholestatic liver injury and intrahepatic ductopenia
Authors: Thio Joel , Haig Adam , Swe Ei Phyu Phyu , Nguyen Paul , Tran Kayla , Kasi Madhavi
Published: July 2024

Artemisinin, an ancient Chinese herbal remedy known colloquially as “Qinghao”, is now used as treatment for malaria as recommended by the World Health Organisation. There have been few reports of artemisinin-induced liver injury. Most of these instances of hepatotoxicity are reportedly due to prolonged use of herbal remedies containing artemisinin. To our knowledge, we report the first case of intrahepatic ductopenia in a patient with cholestatic liver injury after artemisinin use.
Calls to action on lung cancer management and research
Authors: Meyer May-Lucie , Hirsch Fred R , Bunn Paul A , Ujhazy Peter , Fredrickson David , Berg Christine D , Carbone David P , Halmos Balazs , Singh Harpreet , Borghaei Hossein , Ferris Andrea , Langer Corey , Dacic Sanja , Mok Tony S , Peters Solange , Johnson Bruce E
Published: July 2024

Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our “Calls to Action.” The consortium prioritized 8 different calls to action. These include (1) develop strategies to cure more patients with early-stage lung cancer, (2) investigate carcinogenesis leading to lung cancers in patients without a history of smoking, (3) harness precision medicine for disease interception and prevention, (4) implement solutions to deliver prevention measures and effective therapies to individuals in under-resourced countries, (5) facilitate collaborations with industry to collect and share data and samples, (6) create and maintain open access to big data repositories, (7) develop new immunotherapeutic agents for lung cancer treatment and prevention, and (8) invest in research in both the academic and community settings. These calls to action provide guidance to representatives from academia, the pharmaceutical and biotech industries, organizational and regulatory leaders, and patient advocates to guide ongoing and planned initiatives.
Dosimetric and radiobiological advantages from deep inspiration breath-hold and free breath technique for left-sided breast radiation using 3DCRT, IMRT and Rapid Arc methods—a complete assessment
Authors: Dashnamoorthy Sougoumarane , Jeyasingh Ebenezar , Rajamanickam Karthick , Pitchaikannu Venkatraman , Nachimuthu Kathiresan
Published: July 2024

The verification and use of the best treatment approach using 3D conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and Rapid Arc methods for left breast radiation with dosimetric and radiobiological characteristics. The use of custom-built Python software for the estimation and comparison of volume, mean dose, maximum dose, monitor units and normal tissue integral dose along with radiobiological parameters such as NTCP, tumor control probability, equivalent uniform dose and LKB’s effective volume from 3DCRT, IMRT and Rapid Arc planning with deep inspiration with breath holding (DIBH) and free breadth (FB) techniques. Volume growth of three-fourth in DIBH compared with FB causes a decrease in cardiac doses and complications because the left lung expands, pulling the heart away from the chest wall and the treatment area. A tiny area of the left lung was exposed during treatment, which reduced the mean dose. There was little difference in the treatment approaches because the spinal cord was immobile in both techniques. Rapid Arc is the unmatched modality for left-sided breast irradiation with significant patient breath-hold, as shown by the comparison of dosimetric and radiobiological parameters from treatment techniques with a deep inspiration breath-hold approach.
Comparison of the equivalent doses of the eye lenses, thyroid, and mammary gland among three pediatric and one adult anthropomorphic phantom during the chest CT examinations using a 40 mm volume helical scan
Authors: Masuda Takanori , Kiguchi Masao , Fujioka Chikako , Oku Takayuki , Ishibashi Toru , Katsunuma Yasushi , Yoshitake Takayasu , Abe Shuji , Awai Kazuo
Published: July 2024

Equivalent doses for the eye lenses, thyroid, and mammary glands were measured and compared between one adult and three pediatric anthropomorphic phantoms during chest computed tomography (CT) using 40 mm volume helical scan on the Aquilion ONE GENESIS Edition CT equipment. Placing an optically stimulated luminescence dosemeter (OSLD) on the eye lenses, thyroid, and mammary gland, we measured and compared the equivalent dose of OSLD among different phantoms during chest CT using a helical scan. Compared with adults, the equivalent doses to the eye lens, thyroid, and mammary glands were ~81%, 77%, and 63% lower in newborns, 1-year-olds, and 5-year-olds using comparable image noise during chest CT.
Rhizomicrobiomics
Authors: Lynch Jim
Published: July 2024

Rhizomicrobiomics is the study of plant-associated microbes as a strategy for achieving sustainable development goals. With the development of the concept of microbiomes of soil/plant systems, the history leading to this concept over more than a century is reviewed. Microbial growth and community dynamics are discussed from both laboratory and field perspectives. The first use of the term microbiome applied to biological control of plant diseases, but it now seems appropriate to use the specific term rhizomicrobiome to describe the myriads of microbial functions that influence soil health, food production, bioremediation, and climate change. The advance and implications of molecular biology and modern imaging, along with functional analysis of ecosystems from space, coupled with artificial intelligence and machine learning, are indicated as ways to investigate the application of rhizomicrobiomics in achieving the UN Sustainable Development Goals to generate a cleaner planet and secure the future supply of food.
Microbiological safety and antimicrobial resistance profiles of ready-to-eat seafood in Bayelsa, Nigeria
Authors: Omeje Faith I , Beshiru Abeni , Igbinosa Isoken H , Igbinosa Etinosa O
Published: July 2024

The global significance of processed seafood necessitates vigilant monitoring for health risks, particularly in the ready-to-eat (RTE) sector. This study assessed the microbiological safety and antimicrobial resistance (AMR) profiles of 520 RTE seafood samples collected from Bayelsa, Nigeria. Escherichia coli identification was conducted using culture-based and polymerase chain reaction (PCR) methods. The isolates were further characterized using standard bacteriological techniques. PCR screening was employed to detect virulence and resistance genes. Of the processed RTE seafood samples assessed, 12.1% tested positive for E. coli. Extended-spectrum beta-lactamase (ESBL)-producing E. coli accounted for 2.3% of the samples. Various diarrheagenic determinants were identified, with aggregative adherence regulator-activated island (aaiC) and attaching and effacing (eae) being the most prevalent. Higher AMR levels were observed in ESBL-producing strains. Additionally, extracellular virulence factors, biofilm formation, and hydrophobicity assays revealed diverse pathogenic potentials among the isolates. The detection of beta-lactamase AMR genes, such as blaTEM (15.9%), blaCTX−M−15 (3.2%), and blaCTX−M−1 (1.6%), underscores the genetic mechanisms responsible for resistance in E. coli strains recovered from RTE seafood. These findings underscore the need for thorough monitoring and strict control procedures to ensure the safety of RTE seafood and mitigate the risks associated with AMR in food consumption.
Pandemic preparedness—political perspectives
Authors: Brüssow Harald
Published: July 2024

Pandemic preparedness is explored for the antibiotic resistance crisis and the threat of a next viral pandemic. Bacterial pathogens escaping from control by antibiotics are well defined, and resistance develops over decades while a next viral pandemic occurs suddenly with a novel virus. The death toll for resistant bacterial infections is reviewed, and the scientific and economic hurdles to the development of new antibiotics are discussed. Regulatory adaptations and financial push and pull programs to restimulate new antibiotic development are explored. The COVID-19 pandemic caused not only millions of deaths, but also economic losses in excess of 10 trillion US dollars. Coronaviruses and influenza viruses remain usual suspects for new viral pandemics, followed by paramyxoviruses. Viral infections at the animal–human interface in wet markets and in disturbed environments need active virus surveillance programs. Learning lessons from the COVID-19 for non-pharmaceutical interventions is difficult to draw since measures were frequently applied in combination against different variant viruses and against changing population immunity levels. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) clinical trials demonstrated that even under emergency situations clinical trials can rapidly provide solid treatment data. Various novel vaccine approaches were the most efficient control measures for the COVID-19 pandemic. Pandemic preparedness also requires a fact-based discussion both in the public and in parliaments to settle the conflict between individual freedom and necessary restrictions during a pandemic. Mature and educated citizens are needed not only for coping with pandemics but also for creating stress-resistant democratic societies. Learned scientific societies should contribute to this discussion.
Biased Gene Introgression and Adaptation in the Face of Chloroplast Capture in Aquilegia amurensis
Authors: Wang Huaying , Zhang Wei , Yu Yanan , Fang Xiaoxue , Zhang Tengjiao , Xu Luyuan , Gong Lei , Xiao Hongxing
Published: July 2024

—Chloroplast capture, a phenomenon that can occur through interspecific hybridization and introgression, is frequently invoked to explain cytonuclear discordance in plants. However, relatively few studies have documented the mechanisms of cytonuclear coevolution and its potential for driving species differentiation and possible functional differences in the context of chloroplast capture. To address this crucial question, we chose the Aquilegia genus, which is known for having minimal sterility among species, and inferred that A. amurensis captured the plastome of A. parviflora based on cytonuclear discordance and gene flow between the 2 species. We focused on the introgression region and its differentiation from corresponding regions in closely related species, especially its composition in a chloroplast capture scenario. We found that nuclear genes encoding cytonuclear enzyme complexes (CECs; i.e., organelle-targeted genes) of chloroplast donor species were selectively retained and displaced the original CEC genes in chloroplast-receiving species due to cytonuclear interactions during introgression. Notably, the intrinsic correlation of CEC introgression was a greater degree of evolutionary distance for these CECs between A. amurensis and A. parviflora. Terpene synthase activity genes (GO: 0010333) were overrepresented among the introgressed genes, and more than 30% of these genes were CEC genes. These findings support our observations that floral terpene release pattern is similar between A. amurensis and A. parviflora compared with A. japonica. Our study clarifies the mechanisms of cytonuclear coevolution, species differentiation, and functional differences in the context of chloroplast capture and highlights the potential role of chloroplast capture in adaptation.
Encapsulated Predatory Bacteria Efficiently Protect Potato Tubers from Soft Rot Disease
Authors: Sason Gal , Chalegoua Errikos , Pun Manoj , Nussinovitch Amos , Jurkevitch Edouard , Yedidia Iris
Published: July 2024

Soft rot Pectobacteriaceae (SRP) are a group of destructive Gram-negative phytopathogens that can infect a wide range of plant hosts, including potatoes. There are no effective control agents available against SRP, making their management challenging. We have developed a novel approach to protect potato tubers against SRP. It makes use of encapsulated predatory Bdellovibrio bacteriovorus bacteria that, upon release from a polymeric carrier, prey upon SRP. We applied a carrageenan-trehalose-based formulation containing a B. bacteriovorus HD100 predator to prevent soft rot disease development in potato tubers, under various conditions. The dried formulation exhibited very high stability over an 18-month period at room temperature (∼25°C), in contrast to unencapsulated suspensions of the predator, in which viability decreased rapidly below detection level. The rehydrated formulation was as efficient as freshly grown unencapsulated predators and provided high protection in potted potato tubers, displaying an average of 50% reduction in disease parameters (e.g., tissue decay and disease index) under controlled conditions at 7 days postinoculation and planting. The protective effect provided by this formulation was maintained in longer-term trials (28 days) conducted in larger vessels within a net house under natural climate conditions, highlighting its potential for practical application in the field.
The neurovascular coupling response of the aged brain is brain-state dependent
Authors: Zhang Xiao , Tao Lechan , Nygaard Amalie H. , Dong Yiqiu , Hong Xiaoqi , Goddard Carolyn M. , He Chen , Postnov Dmitry , Allodi Ilary , Lauritzen Martin J. , Cai Changsi
Published: July 2024

Brain aging lead to reduced cerebral blood flow and cognitive decline, but how normal aging affects neurovascular coupling (NVC) in the awake brain is unclear. Here, we investigated NVC in relation to calcium changes in vascular mural cells (VMCs) in awake adult and aged mice. We show that NVC responses are reduced and prolonged in the aged brain and that this is more pronounced at the capillary level than in arterioles. However, the overall NVC response, measured as the time integral of vasodilation, is the same in two age groups. In adult, but not in aged mice, the NVC response correlated with Ca2+ signaling in VMCs, while the overall Ca2+ kinetics were slower in aged than in adult mice. In particular, the rate of Ca2+ transport, and the Ca2+ sensitivity of VMCs were reduced in aged mice, explaining the reduced and prolonged vasodilation. Spontaneous locomotion was less frequent and reduced in aged mice as compared to young adult mice, and this was reflected in the ‘slow but prolonged’ NVC and vascular Ca2+ responses. Taken together, our data characterize the NVC in the aged awake brain as slow but prolonged, and underscoring the importance of brain state in understanding age-related mechanisms.
A draft Arab pangenome reference
Authors: Nassir Nasna , Almarri Mohamed A. , Kumail Muhammad , Mohamed Nesrin , Balan Bipin , Hanif Shehzad , AlObathani Maryam , Jamalalail Bassam , Elsokary Hanan , Kondaramage Dasuki , Shiyas Suhana , Kosaji Noor , Satsangi Dharana , Abdelmotagali Madiha Hamdi Saif , Abou Tayoun Ahmad , Ahmed Olfat Zuhair Salem , Youssef Douaa Fathi , Al Suwaidi Hanan , Albanna Ammar , Du Plessis Stefan , Khansaheb Hamda Hassan , Alsheikh-Ali Alawi , Uddin Mohammed
Published: July 2024

Pangenomes represent a significant shift from relying on a single reference sequence to a robust set of assemblies, Arab populations remain significantly underrepresented; hence, we present the first Arab Pangenome Reference (APR) utilizing 53 individuals of diverse Arab ethnicities. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads and 65.46X Hi-C reads yielded contiguous haplotype-phasedde novoassemblies of exceptional quality, with an average N50 of 124.28 Mb. We discovered 111.96 million base pairs of novel euchromatic sequences absent from existing human pangenomes, the T2T-CHM13, GRCh38 reference human genomes, and other public datasets. We identified 8.94 million population-specific small variants and 235,195 structural variants within the Arab pangenome. We detected 883 gene duplications including 15.06% associated with recessive diseases and 1,436 bp of novel mitochondrial pangenome sequence. Our study provides a valuable resource for future genomic medicine initiatives in Arab population and other global populations.
Transient TELC and transmembrane potential in a laser flashed bacteriorhodopsin purple membrane open flat sheet
Authors: Lee James Weifu
Published: July 2024

The transmembrane-electrostatically localized protons/cations charges (TELC, also known as TELP) model may serve as a unified framework to explain a wide range of bioenergetic phenomenon. Transient TELC and transmembrane potential in a laser flash-energized bacteriorhodopsin (bR) purple membrane (PM) open flat sheet are now better analyzed. Under the Heberle et al. 1994 experimental conditions, the number of bR molecules is now calculated to be 8200 per PM open flat sheet with a diameter of 600 nm. With a single-turnover laser flash intensity of 3 mJ/cm2to photoexcite 10% of the bR molecules, the number of laser flash-induced peak TELC density is calculated to be 2900 per µm2of PM, which translates to a peak transient transmembrane potential of 50 mV. The bR protonic outlet protrudes into the liquid phase outside the putative “potential well/barrier”. The observation is in line with the TELP model; but does not support the “potential well/barrier” model. The author encourages research on more relevant protonic cell systems that have transmembrane potential with TELC comprising excess positive charges at one side and excess anions at the other side of the membrane.
Transient cortical Beta-frequency oscillations associated with contextual novelty in high density mouse EEG
Authors: Walsh Callum , Tait Luke , Garcia Garrido Maria , Brown Jonathan T , Ridler Thomas
Published: July 2024

Beta-frequency oscillations (20-30 Hz) are prominent in both human and rodent electroencephalogram (EEG) recordings. Discrete epochs of beta (or Beta2) oscillations are prevalent in the hippocampus and other brain areas during exploration of novel environments. However, little is known about the spatial distribution and temporal relationships of beta oscillations across the cortex in response to novelty. To investigate this, mice fitted with 30-channel EEG-style multi-electrode arrays underwent a single recording session in a novel environment. While changes to spectral properties of cortical oscillations were minimal, there was a profound increase in the rate of beta bursts during the initial part of the recording session, when the environment was most novel. This was true across the cortex but most notable in recording channels situated above the retrosplenial cortex. Additionally, novelty was associated with greater connectivity between retrosplenial areas and the rest of the cortex, specifically in the beta frequency range. However, it was also found that the cortex in general, is highly modulated by environmental novelty. This data further suggests the retrosplenial cortex is an important hub for distinguishing environmental context and highlights the diversity of functions for beta oscillations across the brain, which can be observed using high-density EEG.
Microglia-specific transduction via AAV11 armed with IBA1 promoter and miRNA-9 targeting sequences
Authors: Luo Nengsong , Lin Kunzhang , Cai Yuxiang , Sui Xiaokai , Zhang Zilian , Xing Jiayong , Liu Gangning , Yuan Wenjia , Wang Jie , Xu Fuqiang
Published: July 2024

Microglia, as resident immune cells in the central nervous system (CNS), are closely related to human health and the pathogenesis of various CNS diseases, making them compelling targets for therapeutic interventions. However, functional and therapeutic studies of microglia remain significant challenges largely due to the lack of tools capable of efficiently and specifically transducing microglia. Herein, we evaluated the specificity and efficiency of various adeno-associated virus (AAV) vectors armed with the mIBA1 promoter and miRNA-9 targeting sequences in transducing microglia within the caudate putamen (CPu) brain region, and found that AAV11 mediates more specific and efficient transduction of microglia. Subsequently, we further demonstrated that AAV11 also exhibits high transduction specificity for microglia across various brain areas and within the spinal cord. Finally, by reducing the injection dosage, we employed AAV11 for sparse labeling of microglia. This work provides a promising tool for advancing both the functional investigation and therapeutic targeting of microglia.
Realisation threshold revisited: does the minimum tooth size scale with body size?
Authors: Christensen Mona M. , Laakkonen Juha , Jernvall Jukka
Published: July 2024

Based on his analyses of lynx and brown bear teeth, Björn Kurtén coined the concept of ‘realisation threshold’, the smallest size at which a tooth can form and erupt properly. Kurtén found the smallest sizes of the studied lynx and bear teeth to be 2.5 mm and 3.5 mm, respectively, much larger than for example the smallest rodent teeth known to readily erupt. A recent study comparing developing teeth from shrews to elephants suggested a relatively unchanged theoretical minimum tooth size for mammalian teeth. Together, these studies have left open the question of whether realisation thresholds of teeth are larger in larger mammals than in small ones. In this study, we follow Kurtén’s line of thought and compare the sizes of teeth that are variably present in dentitions, and therefore likely cross the realisation threshold only occasionally. First, we show using published reports that variably present teeth are relatively small in large mammals, but larger than the previously suggested theoretical minimum tooth size. Next, we examine the canines of mares that are known to be variably present. We report one canine that, compared with information found in the literature, is by far the smallest compared to the body size. In conclusion, whereas the variably present teeth tend to be larger in large mammals, there may be overlooked potential for large mammals to develop very small teeth. This information can be helpful in extrapolating findings from common small model organisms, such as mice, to larger mammals, including humans.
Legacy effects of extreme events
Authors: Brueggemeier-Singh Danielle , Vos Matthijs
Published: July 2024

Global change is increasing the intensity of environmental extremes. Abiotic extremes include hotter summers and more intense heatwaves1-2. Biotic extremes include disproportionate increases in herbivory3. Both have well-understood immediate impacts on the plant communities that support life across the globe. However, their longterm effects are difficult to predict, as it is unknown how heat and herbivory differ in the way they create historical legacies. These are changes in a community that still affect dynamics and recovery long after a disturbance has passed. Here we show differences in legacy construction by mild and extreme heatwaves and small- and large-bodied herbivores. We analysed patterns in the population dynamics of a consumer added to replicated primary producer communities after disturbance had ended. We find that the legacy induced by extreme heat drives post-disturbance consumer declines in all replicates. This results in stochastic extinctions as the loss of populations becomes more likely when their density gets close to zero. In contrast, the legacy created by the large-bodied herbivore does not drive extinctions. It diminishes population growth by orders of magnitude across six generations. The observed effects appear after a time-lag that is shorter for extreme heat than for herbivory. Our results show that legacy effects drive complex causal sequences that may involve deterministic and chance components, time-lags, stressor amplification and regime shifts. Insight in how these combine to shape the future is essential for our capacity to accurately forecast and repair the consequences of global change.
HDAC4 Inhibits NMDA Receptor-Mediated Stimulation of Neurogranin Expression
Authors: de Andrés Raquel , Martínez-Blanco Elena , Díez-Guerra F. Javier
Published: July 2024

The coordination of neuronal wiring and activity within the central nervous system (CNS) is crucial for cognitive function, particularly in the context of aging and neurological disorders. Neurogranin (Ng), an abundant forebrain protein, modulates calmodulin (CaM) activity and deeply influences synaptic plasticity and neuronal processing. This study investigates the regulatory mechanisms of Ng expression, a critical but underexplored area for combating cognitive impairment. Utilizing both in vitro and in vivo hippocampal models, we show that Ng expression arises during late developmental stages, coinciding with synaptic maturation and neuronal circuit consolidation of. We observed that Ng expression increases in neuronal networks with heightened synaptic activity and identified GluN2B-containing N-methyl-D-aspartate (NMDA) receptors as key drivers of this expression. Additionally, we discovered that nuclear-localized HDAC4 inhibits Ng expression, establishing a regulatory axis that is counteracted by NMDA receptor stimulation. Analysis of the Ng gene promoter activity revealed regulatory elements between the −2.4 and −0.85 Kbp region, including a binding site for RE1-Silencing Transcription factor (REST), which may mediate HDAC4’s repressive effect on Ng expression. Further analysis of the promoter sequence revealed conserved binding sites for the myocyte enhancer factor-2 (MEF2) transcription factor, a target of HDAC4-mediated transcription regulation. Our findings elucidate the interplay between synaptic activity, NMDAR function, and transcriptional regulation in controlling Ng expression, offering insights into synaptic plasticity mechanisms and potential therapeutic strategies to prevent cognitive dysfunction.
Moderate Cold Stress Enhance Drought Resistance throughCCA1via -an ABA-independent Pathway
Authors: Yang Xue , Liu Yan , Jia Zi-Chang , Li Ming , Hou Xuan-Xuan , Hou Sheng-Qiang , Shi Xi-Long , Gao Bei , Zhang Dao-Yuan , Zhu Fu-Yuan , Chen Mo-Xian , Liu Ying-Gao
Published: July 2024

In nature, plants frequently encounter concurrent stresses, particularly the simultaneous occurrence of cold and drought stress poses a challenge to plants in middle and high latitudes. However, the molecular mechanisms underlying the plants response to this double-stress scenario remain unclear. Although some responses suggest that drought stress can improve cold resistance in plants, through ABA signaling pathways. In our study, we discovered that moderate low temperature treatment significantly enhanced Arabidopsis drought tolerance. Low temperature rapidly triggers the transcription factor CCA1, a prototypical response to cold stress, which inturn directly regulates the expression ofOST1andP5CS1by binding to their promoters. This leads to the premature closure of stomata and accumulation of proline through a non-ABA-dependent pathway even before plants experience drought stress, ultimately improving plant resistance against drought and cold. Moreover, this mechanism is conserved across plant species, and the synergistic resistance mechanism enables perennial plants to survive winter conditions and annual plants to withstand multi-stresses.
Genome report: Genome sequence of the tuliptree scale insect,Toumeyella liriodendri(Gmelin)
Authors: Mongue Andrew J. , Markee Amanda , Grebler Ethan , Liesenfelt Tracy , Powell Erin C.
Published: July 2024

Scale insects are of interest both to basic researchers for their unique reproductive biology and to applied researchers for their pest status. In spite of this interest, there remain few genomic resources for this group of insects. To begin addressing this lack of data, we present the genome sequence of the tuliptree scale insect,Toumeyella liriodendri(Gmelin) (Hemiptera: Coccomorpha: Coccidae). The genome assembly spans 536Mb, with over 96% of sequence assembled into one of 17 chromosomal scaffolds. We characterize roughly 66% of this sequence as repetitive and annotate 16,508 protein coding genes. Then we use the reference genome to explore the phylogeny of soft scales (Coccidae) and evolution of karyotype within the family. We find thatT. liriodendriis an early-diverging soft scale, less closely related to most sequenced soft scales than a species of the family Aclerdidae is. This molecular result bolsters a previous, character-based phylogenetic placement of Aclerdidae within Coccidae. In terms of genome structure,T. liriodendrihas nearly twice as many chromosomes as the only other soft scale assembled to the chromosome level,Ericerus pela(Chavannes). In comparing the two, we find that chromosome number evolution can largely be explained by simple fissions rather than more complex rearrangements. These genomic natural history observations lay a foundation for further exploration of this unique group of insects.
Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice
Authors: Natarajan Duraipandy , Ekambaram Shoba , Tarantini Stefano , Yelahanka Nagaraja Raghavendra , Yabluchanskiy Andriy , Hedrick Andria F , Awasthi Vibhudutta , Subramanian Madhan , Csiszar Anna , Balasubramanian Priya
Published: July 2024

Microvascular endothelial dysfunction, characterized by impaired neurovascular coupling, reduced glucose uptake, blood-brain barrier disruption, and microvascular rarefaction, plays a critical role in the pathogenesis of age-related vascular cognitive impairment (VCI). Emerging evidence points to non-cell autonomous mechanisms mediated by adverse circulating milieu (an increased ratio of pro-geronic to anti-geronic circulating factors) in the pathogenesis of endothelial dysfunction leading to impaired cerebral blood flow and cognitive decline in the aging population. In particular, age-related adipose dysfunction contributes, at least in part, to an unfavorable systemic milieu characterized by chronic hyperglycemia, hyperinsulinemia, dyslipidemia, and altered adipokine profile, which together contribute to microvascular endothelial dysfunction. Hence, in the present study, we aimed to test whether thermogenic stimulation, an intervention known to improve adipose and systemic metabolism by increasing cellular energy expenditure, could mitigate brain endothelial dysfunction and improve cognition in the aging population. Eighteen-month-old old C57BL/6J mice were treated with saline or CL (β3-adrenergic agonist) for 6 weeks followed by functional analysis to assess endothelial function and cognition. CL treatment improved neurovascular coupling responses and rescued brain glucose uptake in aged animals. In addition, CL treatment also attenuated blood-brain barrier leakage and associated neuroinflammation in the cortex of aged animals. More importantly, these beneficial changes in microvascular function translated to improved cognitive performance in radial arm water maze and Y-maze tests. Our results suggest that β3-adrenergic agonist treatment improves multiple aspects of brain microvascular endothelial function and can be potentially repurposed for treating age-associated cognitive decline.
Structural variants underlie parallel adaptation following global invasion
Authors: Battlay Paul , Hendrickson Brandon T , Mendez-Reneau Jonas I , Santangelo James S , Albano Lucas J , Wilson Jonathan , Caizergues Aude E , King Nevada , Puentes Adriana , Tudoran Amelia , Violle Cyrille , Vasseur Francois , Patterson Courtney M , Foster Michael J , Stamps Caitlyn , Innes Simon G , Allio Remi , Angeoletto Fabio , Anstett Daniel N , Anstett Julia , Bucharova Anna , Comerford Mattheau S , David Santiago , Falahati Anbaran Mohsen , Godsoe William , Gonzalez-Lagos Cesar , Gundel Pedro E , Hood Glen Ray , Karousou Regina , Lampei Christian , Lara Carlos , Lazaro-Lobo Adrian , Leandro Deleon , Merritt Thomas JS , Mitchell Nora , Mohammadi Bazargani Mitra , Moles Angela , Murua Maureen , Paule Juraj , Pfeiffer Vera , Raeymaekers Joost AM , Rennison Diana J , Rios Rodrigo S , Rowntree Jennifer K , Schneider Adam C , Stack Whitney Kaitlin , Tamburrino Italo , VanWallendael Acer , Kim Paul Y , Ness Rob W , Johnson Marc TJ , Hodgins Kathryn A , Kooyers Nicholas J
Published: July 2024

Rapid adaptation during invasion has historically been considered limited and unpredictable. We leverage whole-genome sequencing of >2600 plants across six continents to investigate the relative roles of colonization history and adaptation during the worldwide invasion of Trifolium repens. Introduced populations contain high levels of genetic variation with independent colonization histories evident on different continents. Five large structural variants on three chromosomes exist as standing genetic variation within the native range, and exhibit strong signatures of parallel climate-associated adaptation across continents. Common gardens in the native and introduced ranges demonstrate that three structural variants exhibit patterns of selection consistent with local adaptation across each range. Our results provide strong evidence that rapid and parallel adaptation during invasion is caused by large-effect structural variants introduced throughout the world.
Advancing membrane-associated protein docking with improved sampling and scoring in Rosetta
Authors: Samnata Rituparna , Harmalkar Ameya , Prathima Priyamvada , Gray Jeffrey J.
Published: July 2024

The oligomerization of protein macromolecules on cell membranes plays a fundamental role in regulating cellular function. From modulating signal transduction to directing immune response, membrane proteins (MPs) play a crucial role in biological processes and are often the target of many pharmaceutical drugs. Despite their biological relevance, the challenges in experimental determination have hampered the structural availability of membrane proteins and their complexes. Computational docking provides a promising alternative to model membrane protein complex structures. Here, we present Rosetta-MPDock, a flexible transmembrane (TM) protein docking protocol that captures binding-induced conformational changes. Rosetta-MPDock samples large conformational ensembles of flexible monomers and docks them within an implicit membrane environment. We benchmarked this method on 29 TM-protein complexes of variable backbone flexibility. These complexes are classified based on the root-mean-square deviation between the unbound and bound states (RMSDUB) as: rigid (RMSDUB < 1.2 A;), moderately-flexible (1.2 A < RMSDUB < 2.2 A), and flexible targets (RMSDUB > 2.2 A). In a local docking scenario, i.e. with membrane protein partners starting ~10 A apart embedded in the membrane in their unbound conformations, Rosetta-MPDock successfully predicts the correct interface (success defined as achieving 3 near-native structures in the 5 top-ranked models) for 67% moderately flexible targets and 60% of the highly flexible targets, a substantial improvement from the existing membrane protein docking methods. Further, by integrating AlphaFold2-multimer for structure determination and using Rosetta-MPDock for docking and refinement, we demonstrate improved success rates over the benchmark targets from 64% to 73%. Rosetta-MPDock advances the capabilities for membrane protein complex structure prediction and modeling to tackle key biological questions and elucidate functional mechanisms in the membrane environment. The benchmark set and the code is available for public use at github.com/Graylab/MPDock.