bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynactin-1 mediates rescue of impaired axonal transport due to reduced mitochondrial bioenergetics in amyotrophic lateral sclerosis motor neurons
Authors: Dafinca Ruxandra , Tosat-Bitrian Carlota , Carroll Emily , Vahsen Björn F , Gilbert-Jaramillo Javier , Scaber Jakub , Feneberg Emily , Johnson Errin , Talbot Kevin 
Published: October 2024

Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system with complex determinants, including genetic and non-genetic factors. A key pathological signature of ALS is the cytoplasmic mislocalization and aggregation of TDP-43 in affected motor neurons, which is found in 97% of cases. Recent reports have shown that mitochondrial dysfunction plays a significant role in motor neuron degeneration in ALS, and TDP-43 modulates several mitochondrial transcripts. In this study, we used induced pluripotent stem cell-derived motor neurons from ALS patients with TDP-43 mutations and a transgenic TDP-43M337V mouse model to determine how TDP-43 mutations alter mitochondrial function and axonal transport. We detected significantly reduced mitochondrial respiration and ATP production in patient induced pluripotent stem cell-derived motor neurons, linked to an interaction between TDP-43M337V with ATPB and COX5A. A downstream reduction in speed of retrograde axonal transport in patient induced pluripotent stem cell-derived motor neurons was detected, which correlated with downregulation of the motor protein complex, DCTN1/dynein. Overexpression of DCTN1 in patient induced pluripotent stem cell-derived motor neurons significantly increased the percentage of retrograde travelling mitochondria and reduced the percentage of stationary mitochondria. This study shows that ALS induced pluripotent stem cell-derived motor neurons with mutations in TDP-43 have deficiencies in essential mitochondrial functions with downstream effects on retrograde axonal transport, which can be partially rescued by DCTN1 overexpression.
A circuit from lateral hypothalamic to dorsal hippocampal dentate gyrus modulates behavioral despair in mice
Authors: Huang Xin , Hu Shan-Shan , Zhang Qi-Lu , Han Xiao-Meng , Chen Zhi-Gang , Nie Rui-Zhe , Cao Xian , Yuan Dan-Hua , Long Yan , Hong Hao , Tang Su-Su 
Published: October 2024

Abstract
Behavioral despair is one of the clinical manifestations of major depressive disorder and an important cause of disability and death. However, the neural circuit mechanisms underlying behavioral despair are poorly understood. In a well-established chronic behavioral despair (CBD) mouse model, using a combination of viral tracing, in vivo fiber photometry, chemogenetic and optogenetic manipulations, in vitro electrophysiology, pharmacological profiling techniques, and behavioral tests, we investigated the neural circuit mechanisms in regulating behavioral despair. Here, we found that CBD enhanced CaMKIIα neuronal excitability in the dorsal dentate gyrus (dDG) and dDGCaMKIIα neurons involved in regulating behavioral despair in CBD mice. Besides, dDGCaMKIIα neurons received 5-HT inputs from median raphe nucleus (MRN) and were mediated by 5-HT1A receptors, whereas MRN5-HT neurons received CaMKIIα inputs from lateral hypothalamic (LH) and were mediated by AMPA receptors to regulate behavioral despair. Furthermore, fluvoxamine exerted its role in resisting behavioral despair through the LH-MRN-dDG circuit. These findings suggest that a previously unidentified circuit of LHCaMKIIα-MRN5-HT-dDGCaMKIIα mediates behavioral despair induced by CBD. Furthermore, these support the important role of AMPA receptors in MRN and 5-HT1A receptors in dDG that might be the potential targets for treatment of behavioral despair, and explain the neural circuit mechanism of fluvoxamine-resistant behavioral despair.
Paradoxical restoration from complete and persistent atrioventricular block after surgical aortic valve replacement: a case report
Authors: Nishihara Ami , Okabe Yuta , Morizumi Sei , Enomoto Yoshiharu , Yoshida Kentaro 
Published: October 2024

Abstract

Background
One of the most important and relatively frequent complications of aortic valve replacement is atrioventricular block. It typically occurs by direct injury of the infranodal conduction system due to intra-operative manipulation and persists post-operatively, necessitating permanent pacemaker implantation in many cases.

Case summary
A 66-year-old man presented to our hospital after experiencing syncope while walking after drinking. He had experienced two episodes of alcohol-induced syncope several years earlier. His electrocardiogram (ECG) and transthoracic echocardiogram revealed complete atrioventricular block and severe aortic stenosis, respectively. He received a temporary pacemaker on the day of admission and underwent surgical aortic valve replacement on hospital Day 9. The native aortic valve was bicuspid. Unexpectedly, the ECG immediately after aortic valve replacement showed complete restoration of atrioventricular conduction during temporary atrial pacing. The atrioventricular block did not recur, and he was discharged to home on post-operative Day 13.

Discussion
This remarkably rare clinical course, complete restoration from complete and persistent atrioventricular block after surgical aortic valve replacement, can be explained by multifactorial mechanisms: (i) surgical removal of the aortic annulus calcification directly hindering the infranodal conduction system; (ii) relief from the ventricular pressure overload stressing the conduction system within the septum; and (iii) improvement of substantial autonomic dysregulation as manifested by alcohol-sensitive syncope in the present patient, which was a result of unloading of the intraventricular pressure affecting the left ventricular mechanoreceptor.
Evolution from mixed to fixed handedness in mirror-image flowers: insights from adaptive dynamics
Authors: Saltini Marco , Barrett Spencer C H , Deinum Eva E 
Published: October 2024

Abstract
Mirror-image flowers (enantiostyly) involve a form of sexual asymmetry in which a flower’s style is deflected either to the left or right side, with a pollinating anther orientated in the opposite direction. This curious floral polymorphism, which was known but not studied by Charles Darwin, occurs in at least 11 unrelated angiosperm families and represents a striking example of adaptive convergence in form and function associated with cross-pollination by insects. In several lineages, dimorphic enantiostyly (one stylar orientation per plant, both forms occurring within populations) has evolved from monomorphic enantiostyly, in which all plants can produce both style orientations. We use a modelling approach to investigate the emergence of dimorphic enantiostyly from monomorphic enantiostyly under gradual evolution. We show using adaptive dynamics that depending on the balance between inbreeding depression following geitonogamy, pollination efficiency, and plant density, dimorphism can evolve from an ancestral monomorphic population. In general, the newly emergent dimorphic population is stable against invasion of a monomorphic mutant. However, our model predicts that under certain ecological conditions, for example, a decline of pollinators, dimorphic enantiostyly may revert to a monomorphic state. We demonstrate using population genetics simulations that the observed evolutionary transitions are possible, assuming a plausible genetic architecture.
Biodiversity of microorganisms in the Baltic Sea: the power of novel methods in the identification of marine microbes
Authors: Mazur-Marzec Hanna , Andersson Anders F , Błaszczyk Agata , Dąbek Przemysław , Górecka Ewa , Grabski Michał , Jankowska Katarzyna , Jurczak-Kurek Agata , Kaczorowska Anna K , Kaczorowski Tadeusz , Karlson Bengt , Kataržytė Marija , Kobos Justyna , Kotlarska Ewa , Krawczyk Beata , Łuczkiewicz Aneta , Piwosz Kasia , Rybak Bartosz , Rychert Krzysztof , Sjöqvist Conny , Surosz Waldemar , Szymczycha Beata , Toruńska-Sitarz Anna , Węgrzyn Grzegorz , Witkowski Andrzej , Węgrzyn Alicja 
Published: October 2024

Abstract
Until recently, the data on the diversity of the entire microbial community from the Baltic Sea were relatively rare and very scarce. However, modern molecular methods have provided new insights into this field with interesting results. They can be summarized as follows. (i) Although low salinity causes a reduction in the biodiversity of multicellular species relative to the populations of the North–East Atlantic, no such reduction occurs in bacterial diversity. (ii) Among cyanobacteria, the picocyanobacterial group dominates when considering gene abundance, while filamentous cyanobacteria dominate in means of biomass. (iii) The diversity of diatoms and dinoflagellates is significantly larger than described a few decades ago; however, molecular studies on these groups are still scarce. (iv) Knowledge gaps in other protistan communities are evident. (v) Salinity is the main limiting parameter of pelagic fungal community composition, while the benthic fungal diversity is shaped by water depth, salinity, and sediment C and N availability. (vi) Bacteriophages are the predominant group of viruses, while among viruses infecting eukaryotic hosts, Phycodnaviridae are the most abundant; the Baltic Sea virome is contaminated with viruses originating from urban and/or industrial habitats. These features make the Baltic Sea microbiome specific and unique among other marine environments.
Validity of a visual analogue scale to measure and value the perceived level of sanitation: evidence from Ghana and Mozambique
Authors: Cheung Ho Hei , Adriano Zaida , Dwumfour-Asare Bismark , Nyarko Kwabena B , Scott Pippa , Nala Rassul , Brown Joe , Cumming Oliver , Ross Ian 
Published: October 2024

Abstract
Two billion people globally lack access to a basic toilet, and sanitation is a critical determinant of health and well-being. Evaluations of sanitation programmes typically measure disease or behaviour, and visual analogue scales (VASs) have not been used to measure users’ feelings about their level of sanitation. In this study, we assess the validity of a horizontal sanitation VAS numbered 0–10, with end anchors ‘best imaginable’ and ‘worst imaginable’ sanitation. In Kumasi, Ghana, we surveyed 291 participants before and after uptake of a container-based sanitation service. In Maputo, Mozambique, we surveyed 424 participants from treatment groups of a prior trial. We assessed construct validity by testing hypothesized associations between VAS scores and toilet characteristics and by respondents valuing three hypothetical sanitation states. We assessed responsiveness by comparing VAS with/without sanitation interventions. There was evidence (P &lt; 0.05) for 60% of hypothesized associations in Ghana and 100% in Mozambique. For responsiveness, there was a 3.4-point increase (2.1 SD) in VAS 10 weeks post-intervention in Ghana and a 2.9 point difference (1.3 SD) in Mozambique. In valuation exercises, the mean was higher (P &lt; 0.001) for the objectively better sanitation state. The sanitation VAS could be useful in economic evaluation to identify which improvements achieve quality-of-life gains most efficiently. For future studies, we recommend a vertical sanitation VAS numbered 0–100 with emojis at end anchors but retaining a 0–10 option for those who struggle with numeracy.
Circadian rhythms of microbial communities and their role in regulating nitrogen and phosphorus cycling in the rhizosphere of tea plants
Authors: Liu Miao , Wang Junhua , Li Zhengzhen , Li Xin , Korpelainen Helena , Li Chunyang 
Published: October 2024

Abstract
The circadian clock mediates metabolic functions of plants and rhythmically shapes structure and function of microbial communities in the rhizosphere. However, it is unclear how the circadian rhythm of plant hosts regulates changes in rhizosphere bacterial and fungal communities and nutrient cycles. In the present study, we measured diel changes in the rhizosphere of bacterial and fungal communities, and in nitrogen (N) and phosphorus (P) cycling in 20-year-old tea plantations. The fungal communities were more stable in their responses to circadian changes than bacterial communities in the rhizosphere of the cultivars LJ43 and ZC108. Nevertheless, fungal genera with circadian rhythms were more numerous and had a higher abundance at midnight. Organic P and N mineralization in the rhizosphere was more intensive in LJ43 under day–night alterations, while inorganic N and P cycling was more easily affected by circadian rhythms in ZC108. The rhizosphere denitrification encoded by the genes AOA and AOB was intensive in the morning, irrespective of tea cultivar. Genes related to rhizosphere N fixation (nifH) and denitrification (nosZ and nirK) expressed at greater levels in ZC108, and they reached a peak at midnight. Moreover, the diel rhythm of rhizosphere microbial communities in ZC108 largely regulated dial changes in N and P cycling. These results suggested that the bacterial and fungal communities in the rhizosphere respond differently to circadian rhythms, and they vary between tea cultivars. The timing of bacterial and fungal cycling largely regulates rhizosphere N and P cycling and their ecological functions.
CRISPR/Cas9-mediated CHS2 mutation provides a new insight into resveratrol biosynthesis by causing a metabolic pathway shift from flavonoids to stilbenoids in Vitis davidii cells
Authors: Lai Gongti , Fu Peining , He Liyuan , Che Jianmei , Wang Qi , Lai Pufu , Lu Jiang , Lai Chengchun 
Published: October 2024

Abstract
Resveratrol is an important phytoalexin that adapts to and responds to stressful conditions and plays various roles in health and medical therapies. However, it is only found in a limited number of plant species in low concentrations, which hinders its development and utilization. Chalcone synthase (CHS) and stilbene synthase (STS) catalyze the same substrates to produce flavonoids and resveratrol, respectively. However, it remains unclear how CHS and STS compete in metabolite synthesis. In this study, two CHS2 mutant cell lines (MT1 and MT2) were generated using CRISPR/Cas9 genome editing. These CHS2 mutant cell lines exhibited abundant mutations in CHS2, leading to the premature termination of protein translation and subsequent CHS2 knockout. Amplicon sequencing confirmed comprehensive CHS2 knockout in MT1, whereas the wild-type sequence remained predominant in the MT2 cell line. Transcriptome and RT-qPCR results showed a significant downregulation of genes involved in flavonoid biosynthesis, including CHS2, CHS3, F3H, F3’H, DFR, FLS, LDOX, among others, resulting in decreased flavonoid accumulation, such as anthocyanins, proanthocyanidins, quercetin, and kaempferol. Conversely, STS genes involved in stilbenoid biosynthesis were upregulated competing with the flavonoid pathway. Consequently, there was a marked increase in stilbenoids, including resveratrol, piceatannol, piceid, and pterostilbene, with a 4.1-fold increase in resveratrol and a 5.3-fold increase in piceid (a derivative of resveratrol) observed in CHS2 mutant cell lines. This research demonstrates that CHS2 mutation induces a shift from flavonoid biosynthesis towards stilbenoid biosynthesis, offering new insights into metabolite biosynthesis and regulation, as well as an alternative solution for natural resveratrol production, and a novel breeding approach for eliminating non-target agronomic traits using CRISPR-Cas9.
Resistance is reality: findings from the first Ukrainian cumulative antibiogram
Authors: Vodianyk Arkadii , Holovnia Oksana , Diomin Eugene , Letourneau Alyssa R , Poznansky Mark C , Shenoy Erica S , Turbett Sarah E 
Published: October 2024

Abstract

Background
Antimicrobial resistance is a global health threat resulting in significant morbidity and mortality worldwide. Until recently, in Ukraine, cumulative antibiograms (CuAbgms) have never been available.

Objectives
To describe the first CuAbgm developed in Ukraine.

Methods
We developed a CuAbgm for the Okhmatdyt National Specialized Children’s Hospital using data from WHONET. Antimicrobial susceptibility testing was performed per EUCAST guidelines. The CuAbgm was developed using guidance from CLSI.

Results
For Escherichia coli, 66% and 69% of isolates were susceptible to ceftazidime and ceftriaxone, respectively, and 99% were susceptible to meropenem. For Klebsiella pneumoniae, 26% and 27% of isolates were susceptible to ceftazidime and ceftriaxone, respectively, and only 59% were susceptible to meropenem. Of the carbapenem-resistant K. pneumoniae isolates that underwent additional susceptibility testing, only 38% were susceptible to ceftazidime/avibactam. For Pseudomonas aeruginosa, only 53% were susceptible to meropenem. Of those that were resistant to meropenem and underwent additional susceptibility testing, only 12% were susceptible to ceftazidime/avibactam. Similarly, for Acinetobacter spp., only 37% of isolates were susceptible to meropenem. Susceptibility to ampicillin/sulbactam was also low at 45%. The oxacillin susceptibility rate for Staphylococcus aureus was 99%.

Conclusions
In this first-ever CuAbgm developed in Ukraine, high levels of resistance were demonstrated among Gram-negative bacteria. CuAbgms should be prioritized in laboratories in Ukraine to guide empirical antimicrobial therapy, infection control and antimicrobial stewardship policies. This is of heightened relevance during wartime, when there is a need for healthcare systems to treat complex and infected penetrating and blast-related injuries.
Forsythoside B, the active component of Frosythiae fructuse water extract, alleviates Streptococcus pneumoniae virulence by targeting pneumolysin
Authors: Wang Zhongtian , Sun Yingying , Gu Kuan , Tong Yue , Liu Huanyu , Wang Lei , Tan Tianhui , Yang Fushuang , Ren Xiaoting , Ding Lizhong , Sun Liping , Wang Lie 
Published: October 2024

Abstract

Aims
To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage.

Methods and results
Hemolysis tests were used to evaluate Forsythoside B’s inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections.

Conclusions
Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae.
Seminal plasma uterine priming alters uterine transcriptomics and negatively impacts embryo growth and uterine artery resistance but not offspring liver transcriptomics in beef cattle
Authors: Swanson Rebecca M , Messman Riley D , Dobbins Thomas W , Contreras-Correa Zully E , Arick Mark A , Sidelinger Darcie R , King Heath , Lemley Caleb O 
Published: October 2024

Abstract
Seminal plasma uterine priming is important for pregnancy and offspring phenotype in mice and swine; however, impacts on the uterus of the dam and her offspring in cattle are unknown. We sought to determine the effects of seminal plasma uterine priming at estrus on uterine transcriptomics, early gestation (days 35, 40, and 45) embryo morphometrics, mid- to late-gestation (days 140 to 220) uterine artery hemodynamics, birth morphometrics, and liver transcriptomics in offspring at 30 d of age. Multiparous Angus-based commercial beef cows were randomly assigned to receive treatment at estrus: 0.5 mL pooled seminal plasma in the uterine body (n = 31, seminal plasma primed) or no treatment (n = 31, control). Seven days later a subset of cows (n = 4/treatment) underwent uterine biopsies, and the remaining cows underwent embryo transfer. Embryo crown-rump length and uterine artery hemodynamics were measured during gestation using ultrasonography. Morphometrics of the calf were collected within 24 h of parturition. Liver biopsies were collected at 30 d of age. Data were analyzed by analysis of variance (ANOVA) in a completely randomized design for the effect of treatment. Myosin heavy chain I (JSP.1) was downregulated [Benjamin–Hochberg adj P (BH) ≤ 0.05] and ABO alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO) was upregulated (BH adj P ≤ 0.05) in the uterus of seminal plasma primed cows 7 d after treatment. Embryo crown-rump length was less (P &lt; 0.05) in seminal plasma primed cows. Mid- to late-gestation (days 140 to 220) uterine artery resistance was increased (P &lt; 0.05) in seminal plasma primed cows. Seminal plasma priming did not alter birth weights or curve-crown-rump length, but heart girth was increased (P &lt; 0.05) in offspring from seminal plasma primed cows. There were no differentially expressed genes (BH adj P ≤ 0.05) in offspring liver at 30 d of age; however, myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF) was absent in all liver samples from calves from seminal plasma primed cows. In contrast, vomeronasal 1 receptor bosTauV1R414 (BOSTAUV1R414) was present in 6 of the 7 liver samples from calves from seminal plasma primed cows. Seminal plasma uterine priming alters uterine transcriptomics, negatively impacts early gestation embryo growth, and mid- to late-gestation uterine artery resistance suggesting downstream vascular anomalies. However, these in utero conditions did not impact offspring from birth to 30 d of age.