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Recent decades have witnessed significant progress in understanding mechanisms driving neurodegeneration and disease progression in multiple sclerosis (MS), but with a focus on the cerebrum. In contrast, there have been limited studies of cerebellar disease, despite the common occurrence of cerebellar symptoms in this disorder. These rare studies, however, highlight the early cerebellar involvement in disease development and an association between the early occurrence of cerebellar lesions and risk of worse prognosis. In parallel developments, it has become evident that far from being a region specialized in movement control, the cerebellum plays a crucial role in cognitive function, via circuitry connecting the cerebellum to association areas of the cerebrum. This complexity, coupled with challenges in imaging of the cerebellum have been major obstacles in the appreciation of the spatio-temporal evolution of cerebellar damage in MS and correlation with disability and progression. MS studies based on animal models have relied on an induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE), in rodents and non-human primates (NHP). EAE has played a critical role in elucidating mechanisms underpinning tissue damage and been validated for the generation of proof-of-concept for cerebellar pathological processes relevant to MS. Additionally, rodent and NHP studies have formed the cornerstone of current knowledge of functional anatomy and cognitive processes. Here, we propose that improved insight into consequences of cerebellar damage in MS at the functional, cellular and molecular levels would be gained by more extensive characterization of EAE cerebellar pathology combined with the power of experimental paradigms in the field of cognition. Such combinatorial approaches would lead to improved potential for the development of MS sensitive markers and evaluation of candidate therapeutics.

Abstract Cooperative breeding, which is commonly characterized by nonbreeding individuals that assist others with reproduction, is common in avian species. However, few accounts have been reported in Charadriiformes, particularly island‐nesting species. We present incidental observations of cooperative breeding behaviors in the Hawaiian Stilt (Himantopus mexicanus knudseni), an endangered subspecies of the Black‐necked Stilt (Himantopus mexicanus), during the 2012–2020 nesting seasons on the Hawaiian islands of O‘ahu and Moloka‘i. We describe two different behaviors that are indicative of cooperative breeding: (a) egg incubation by multiple adults; (b) helpers‐at‐the‐nest, whereby juveniles delay dispersal and reproduction to assist parents and siblings with reproduction. These observations are the first published accounts of cooperative breeding in this subspecies and merit further investigation, as cooperative breeding may improve population viability of the endangered, endemic Hawaiian Stilt.

Invasive predator control is often critical to improving the nesting success of endangered birds, but methods of control vary in cost and effectiveness. Poison-baiting or trapping and removal are relatively low-cost, but may have secondary impacts on non-target species, and may not completely exclude mammals from nesting areas. Mammal-exclusion fencing has a substantial up-front cost, but due to cost savings over the lifetime of the structure and the complete exclusion of mammalian predators, this option is increasingly being utilized to protect threatened species such as ground-nesting seabirds. However, non-mammalian predators are not excluded by these fences and may continue to impact nesting success, particularly in cases where the fence is designed for the protection of waterbirds, open to an estuary or wetland on one side. Thus, there remains a research gap regarding the potential gains in waterbird nesting success from the implementation of mammal-exclusion fencing in estuarine systems. In this study, we compared the nesting success of endangered Hawaiian Stilts (Ae‘o; Himantopus mexicanus knudseni) within a mammal-exclusion fence to that of breeding pairs in a nearby wetland where trapping was the sole means for removing invasive mammals. We predicted success would be greater for breeding pairs inside the exclusion fence and the hatchlings inside the enclosure would spend more time in the nesting area than hatchlings at the unfenced site. During a single breeding season following construction of a mammal-exclusion fence, we used motion-activated game cameras to monitor nests at two sites, one site with mammal-exclusion fencing and one site without. Clutch sizes and hatch rates were significantly greater at the fenced site than the unfenced site, but time spent by chicks in the nesting area did not differ between sites. These results add to the mounting body of evidence that demonstrates the effectiveness of mammal-exclusion fencing in protecting endangered birds and suggests it can aid endangered Hawaiian waterbirds toward recovery. These results also suggest that the single greatest predatory threat to the Hawaiian Stilt may be invasive mammals, despite a host of known non-mammalian predators including birds, crabs, turtles, and bullfrogs, as the complete exclusion of mammals resulted in significant gains in nesting success. As additional fences are built, future studies are necessary to compare nesting success among multiple sites and across multiple seasons to determine potential gains in fledging success and recruitment.

Abstract The olive flounder, Paralichthys olivaceus, also known as the Korean halibut, is an economically important flatfish in East Asian countries. Here, we provided four fully phased genome assemblies of two different olive flounder individuals using high-fidelity long-read sequencing and their parental short-read sequencing data. We obtained 42–44 Gb of ~15-kb and ~Q30 high-fidelity long reads, and their assembly quality values were ~53. We annotated ~30 K genes, ~170-Mb repetitive sequences, and ~3 M 5-methylcytosine positions for each genome assembly, and established a graph-based draft pan-genome of the olive flounder. We identified 5 M single-nucleotide variants and 100 K structural variants with their genotype information, where ~13% of the variants were possibly fixed in the two Korean individuals. Based on our chromosome-level genome assembly, we also explored chromosome evolution in the Pleuronectiformes family, as reported earlier. Our high-quality genomic resources will contribute to future genomic selection for accelerating the breeding process of the olive flounder.

Abstract The human cutaneous lymphatic system strictly controls lymphatic functions by coordinating with skin cells. The lymphatic system plays important roles in removing cell waste, residual proteins, various antigens, and immune cells from tissues to maintain homeostasis and activate the immune system through the drainage of interstitial fluid1,2. The skin protects our body from external stimuli such as pathogens through the cutaneous lymphatic system3,4. Herein, to develop an in vitro human cutaneous lymphatic model, we present two 3D microfluidic platforms: a lymphangiogenesis model with a precollecting lymphatic vessel-like structure and an advanced lymphangiogenesis model with a functional cutaneous barrier and a precollecting lymphatic vessel-like structure. In addition, we rapidly analyzed prolymphangiogenic effects using methods that incorporate a high-speed image processing system and a deep learning-based vascular network analysis algorithm by 12 indices. Using these platforms, we evaluated the pro-lymphangiogenic effect of Lymphanax, a natural product derived from fresh ginseng. As a result, we demonstrated that Lymphanax induces robust lymphangiogenesis without any structural abnormalities. In conclusion, we suggest that these innovative platforms are useful for studying the interaction between the skin and lymphatic system as well as evaluating the prolymphangiogenic effects of drugs and cosmetics.

This study identified the effects of substituting fishmeal (FM) with soy protein concentrate (SPC) supplemented with lysine and methionine in the olive flounder (Paralichthys olivaceus) diet on the expression of genes related to growth, stress, immunity, and digestion. Three experimental diets were prepared; the control diet (Con) contained 60% FM, and the experimental diets contained 25% (SPC25) and 50% (SPC50) FM replaced by SPC. After the 140-day feeding period, weight gain, specific growth rate, feed availability, biological indices, and chemical composition of the muscle were not significantly affected by the dietary treatments. The gene expression levels of growth-related genes (IGF, GFB-3), immune-related genes (IL-8 and caspase), and stress-related genes (SOD, GPX, PRX, TRX) were higher in Con fish than in those fed the SPC25 and SPC50 diets. Chymo-TRY2, TRY2, and TRY3 in the stomach of fish fed the SPC25 diet were higher than fish fed the Con or SPC50 diets. TRY2 and lipase of fish fed the SPC25 diet were higher than those of fish fed the other diets but TRY3 was not significantly affected by the treatments in the intestine. In conclusion, substituting 25% FM with SPC was the most effective diet for the expression of growth, immune, stress, and digestive enzyme genes.

Ferroptosis, a novel form of regulated cell death characterized by dependence on iron and lipid peroxidation, has been implicated in a wide range of clinical conditions including neurological diseases, cardiovascular disorders, acute kidney failure, and various types of cancer. Therefore, it is critical to suppress cancer progression and proliferation. Ferroptosis can be triggered in cancer cells and some normal cells by synthetic substances, such as erastin, Ras-selective lethal small molecule-3, or clinical pharmaceuticals. Natural bioactive compounds are traditional drug discovery tools, and some have been therapeutically used as dietary additives or pharmaceutical agents against various malignancies. The fact that natural products have multiple targets and minimal side effects has led to notable advances in anticancer research. Research has indicated that ferroptosis can also be induced by natural compounds during cancer treatment. In this review, we focused on the most recent developments in emerging molecular processes and the significance of ferroptosis in cancer. To provide new perspectives on the future development of ferroptosis-related anticancer medications, we also provide a summary of the implications of natural phytochemicals in triggering ferroptosis through ROS production and ferritinophagy induction in a variety of malignancies.

Breast cancer presents a significant global health challenge with rising incidence rates worldwide. Despite current efforts, it remains inadequately controlled. Functional foods, notably tempeh, have emerged as promising candidates for breast cancer prevention and treatment due to bioactive peptides and isoflavones exhibiting potential anticancer properties by serving as antioxidants, inducing apoptosis, and inhibiting cancer cell proliferation. This study integrates pharmacoinformatics and cellular investigations (i.e., a multifaceted approach) to elucidate the antioxidative and anti-breast cancer properties of tempeh-derived isoflavones. Methodologies encompass metabolomic profiling, in silico analysis, antioxidant assays, and in vitro experiments. Daidzein and genistein exhibited potential therapeutic options for breast cancer treatment and as antioxidant agents. In vitro studies also supported their efficacy against breast cancer and their ability to scavenge radicals, particularly in soy-based tempeh powder (SBT-P) and its isoflavone derivatives. Results have demonstrated a significant downregulation of breast cancer signaling proteins and increased expression of miR-7-5p, a microRNA with tumor-suppressive properties. Notably, the LD50 values of SBT-P and its derivatives on normal breast cell lines indicate their potential safety, with minimal cytotoxic effects on MCF-10A cells compared to control groups. The study underscores the favorable potential of SBT-P as a safe therapeutic option for breast cancer treatment, warranting further clinical exploration.

Linked article: This is a response to the comment by Lei et al. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Ubiquitin-40S ribosomal protein S27a (RPS27A), ubiquitin-like protein Fubi, and ribosomal protein (S30FAU) are ubiquitin-related proteins that are involved in the regulation of immune-related functions such as cell cycle, protein expression, and apoptosis. This study aimed to confirm the molecular characteristics, gene expression analysis, and antibacterial activity of RPS27A and S30FAU identified from the starry flounder (15 starry flounders of 128.7 ± 18.2 g). An expression analysis using a normal fish showed that RPS27A was highly expressed in the head kidney, heart, and stomach. In contrast, S30FAU exhibited high expression in the stomach, heart, and head kidney. Upon simulating an artificial pathogen infection, RPS27A was highly expressed in the heart at 1 h and 3 days post-viral hemorrhagic septicemia (VHSV) infection, and had a high expression in the kidney, liver, and heart at 7 days post-Streptococcus parauberis (S. parauberis) infection. S30FAU was highly expressed in the spleen and gills at 1 day and 12 h post-VHSV infection, respectively, and exhibited a high expression in the kidney at 7 days post-S. parauberis infection. In an MIC analysis, RPS27A and S30FAU showed antimicrobial activity against all bacteria used in this study. In the biofilm assay, S30FAU was removed from S. parauberis in a concentration-dependent manner, and the cytotoxicity test showed no hemolytic activity in both RPS27A and S30FAU. Therefore, RPS27A and S30FAU of the starry flounder were confirmed to possess antimicrobial peptide abilities without limitations of cytotoxicity. This study provides valuable information on the antibacterial ability and molecular biology of the ubiquitin family isolated from the starry flounder.

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

Olive flounder (Paralichthys olivaceus) is a vital aquaculture species in East Asia. However, few studies that estimate the genetic parameters of this species have been conducted. We estimated the genetic parameters of growth traits and designed an optimum breeding programme for this species. Heritability, genetic and phenotypic correlations, and breeding values were estimated for growth traits: body weight (BW), total length (TL), and condition factor (CF). A linear mixed animal model using the restricted maximum likelihood (REML) algorithm was applied to the statistical analysis of 9 traits (BW, TL, and CF at 11, 18, and 22 months of age) for a total of 54,159 animals from 7 generations. Increases of 13%, 8%, and 6.5% in BW, TL, and CF at the harvest stage were observed, respectively, after 7 generations of selection. The heritabilities of all growth traits were moderate, ranging from 0.35 to 0.46. The phenotypic and genetic correlations between BW and TL were high and positive in all three stages (0.91 and 0.92, 0.91 and 0.93, and 0.88 and 0.91). The estimated breeding values of BW and TL increased over the generations; however, the estimated breeding value of CF fluctuated. The optimum progeny number within full-sib families for an accuracy of 0.632 is suggested to be between 10 and 25. Findings indicated that a considerable response to selection and single-trait selection based on BW would be effective in olive flounder.

Our objective was to assess the reported reasons for episiotomy performance in Israel and to review the relevant professional literature. Using anonymous questionnaires, a survey was conducted among obstetricians and midwives in four northern Israel hospitals, and the accoucheurs were asked to score their agreement with 13 proposed indications for episiotomy. Overall, 84 doctors and 32 midwives completed the questionnaires. 86.1% of the responders reported performing episiotomy in all or most cases of shoulder dystocia, and more than half reported performing it in most cases of vacuum deliveries, fetal macrosomia and advanced perineal tear in previous delivery. Subjective assessment of perineal characteristics constituted a justified reason for episiotomy for 15.8–43.9% of the accoucheurs. In conclusion, there is a wide variation in reported reasons for episiotomy between the obstetricians, and many of these indications are not congruent with international practice guidelines. Uniform protocols and educational programmes are needed to guide episiotomy practice. [ABSTRACT FROM PUBLISHER]

Shrimp is one of the most valuable aquaculture species globally, and the most internationally traded seafood product. Consequently, shrimp aquaculture practices have received increasing attention due to their high value and levels of demand, and this has contributed to economic growth in many developing countries. The global production of shrimp reached approximately 6.5 million t in 2019 and the shrimp aquaculture industry has consequently become a large-scale operation. However, the expansion of shrimp aquaculture has also been accompanied by various disease outbreaks, leading to large losses in shrimp production. Among the diseases, there are various viral diseases which can cause serious damage when compared to bacterial and fungi-based illness. In addition, new viral diseases occur rapidly, and existing diseases can evolve into new types. To address this, the review presented here will provide information on the DNA and RNA of shrimp viral diseases that have been designated by the World Organization for Animal Health and identify the latest shrimp disease trends.

Regions of Homozygosity (ROH) typically reflect normal demographic history of a human population, but may also relate to cryptic consanguinity, and, additionally, have been associated with specific medical conditions. The objective of this study was to investigate the location, size, and prevalence of common ROH segments in a Middle Eastern cohort. This retrospective study included 13 483 samples collected from all Chromosomal Microarray analyses (CMA) performed using Single Nucleotide Polymorphism (SNP) arrays at the genetic clinical laboratory of Rabin Medical Center between 2017-2023 (primary data set). An additional replication cohort including 100 842 samples from another SNP array platform, obtained from Maccabi Health Organization, was analyzed. Common ROH locations were defined as those ROH locations involving 1% or more of the samples. A total of 66 710 ROH segments, involving 13 035 samples (96.7%) were identified in the primary data set. Of the 4069 cytogenetic ROH locations, 68 were identified as common. The prevalence of non-common ROH was relatively high in affected individuals, and for acrocentric chromosomes, chromosomes associated with common trisomies, and non-imprinted chromosomes. In addition, differences in common ROH locations were observed between the primary and the replication cohorts. Our findings highlight the need for population-specific guidelines in determining ROH reporting cutoffs, considering factors such as population-specific prevalence and testing platform differences. Future research with larger, varied cohorts is essential to advance understanding of ROH's associations with medical conditions and to improve clinical practices accordingly., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Obstetric anal sphincter injuries (OASIS) pose significant challenges for young women following childbirth. The association between mediolateral episiotomy and OASIS remains a subject of debate and uncertainty. This study seeks to fill this gap., Methods: This retrospective cohort study was performed using electronic database of obstetrics department at a tertiary medical center. All vaginal deliveries and vacuum-assisted deliveries at term, with a singleton live fetus at cephalic presentation between 2015 and 2021, were included. A comparison of the rates of mediolateral episiotomy and OASIS was conducted between the periods 2015-2017 and 2018-2021. Subgroup analysis was carried out based on parity and the mode of delivery., Results: Overall, the study included 18,202 women. Between 2015 and 2017, episiotomy was performed in 1,272 cases (17.5 %), compared to 1,241 cases (11.4 %) between 2018 and 2021 (p<0.0001). Conversely, a significant increase in OASIS was observed, rising from 0.3 % during 2015-2017 to 0.6 % during 2018-2021 (p=0.012). Multivariable analysis unveiled two factors significantly linked to OASIS: the temporal cohort studied, indicating an increasing trend in recent years, and the utilization of epidural analgesia, which exhibited a protective effect, while episiotomy was not associated with OASIS., Conclusions: Our findings indicate a marked decline in the utilization of episiotomy over the study period, accompanied by an increase in OASIS incidence. Nevertheless, our analysis found no statistically significant link between episiotomy use and OASIS incidence., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Long contiguous stretches of homozygosity or regions of homozygosity (ROH) are frequently detected via microarray and sequencing technologies. However, consensus on the establishment of specific size cutoffs for reporting ROH remains elusive. This study aims to assess the Total ROH Percentages (TRPS) and size of ROH segments across different ethnic origins, exploring potential disparities and proposing tailored diagnostic thresholds. This retrospective study included 13,035 microarray analyses conducted between 2017 to 2023. ROH segments on autosomal chromosomes were retrieved, and samples lacking ROH segments were excluded. The cohort was categorized based on reported ethnic origins, and TRPS and ROH segment size were analyzed for each origin. Distinct TRPS values were noted among different ethnic groups, ranging from median 0.36% in Ethiopian Jewish cohort and up to 6.42% in the Bedouin population. Wide range of 99th percentiles of ROH segment size for various origins was noted, ranging from 10.6 to 51.5 Mb. A significant correlation between ROH segment sizes and TRPS was noted in each origin. Statistically significant differences in ROH segment sizes were noted between the Jewish and the Israeli Arab/Druze origins in TRPS from 1% to 9.99%, whereas extremities of low (0.11%-0.99%) and high (over 10%) TRPS yielded no significant differences. In conclusion, as fixed absolute size thresholds may overlook pathogenic segments in certain populations while generating excessive reports in others, tailored approaches to define ROH reporting thresholds can be considered to facilitate the accuracy and clinical relevance of genomic analyses., (© 2024 Wiley Periodicals LLC.)

Objective: The aim of this study was to assess the usefulness of routine hemoglobin testing following elective and urgent cesarean section (CS) in patients without primary postpartum hemorrhage (PPH)., Methods: This retrospective cohort study included women who underwent vaginal delivery (VD), elective CS, and urgent CS at Carmel Medical Center from 2015 to 2020. Data were extracted from the obstetric database, excluding deliveries with PPH. Demographic and obstetric variables were recorded. Primary outcomes were the need for packed red blood cell transfusion., Results: A total of 19 446 women were included, with five (0.3%) requiring a blood transfusion in the elective CS group, 27 (0.17%) in the VD group, and eight (0.4%) in the urgent CS group. Urgent CS was associated with a higher risk of blood transfusion, but there was no significant difference between elective CS and VD. Elective CS showed the lowest rates of post-delivery hemoglobin below 7 g/dL 1 (0.1%) compared to VD 16 (0.6%) and urgent CS 13 (0.7%)., Conclusion: Routine postoperative hemoglobin testing following elective CS in asymptomatic patients without PPH appears unnecessary. This study supports reconsidering routine hemoglobin testing following elective CS, aligning with the goal of optimizing resource utilization while maintaining patient quality., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)