Multi-omics Analysis of Umbilical Cord Hematopoietic Stem Cells from a Multi-ethnic Cohort of Hawaii Reveals the Transgenerational Effect of Maternal Pre-Pregnancy Obesity.

Background: Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018).

Results: Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.

Oocyte-specific EXOC5 expression is required for mouse oogenesis and folliculogenesis.

EXOC5 is a crucial component of a large multi-subunit tethering complex, the exocyst complex, that is required for fusion of secretory vesicles with the plasma membrane. Exoc5 deleted mice die as early embryos. Therefore, to determine the role of EXOC5 in follicular and oocyte development, it was necessary to produce a conditional knockout (cKO), Zp3-Exoc5-cKO, in which Exoc5 was deleted only in oocytes.

Combinations of the azaquinazoline anti- agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis.

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti- azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: CB.

Low levels of mouse sperm chromatin fragmentation delay embryo development.

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner.

The 2022 Hunga-Tonga megatsunami: Near-field simulation of a once-in-a-century event.

The Hunga Tonga-Hunga Ha'apai (HTHH) volcanic eruption in January 2022 generated catastrophic tsunami and contends for the largest natural explosion in more than a century. The main island, Tongatapu, suffered waves up to 17 m, and Tofua Island suffered waves up to 45 m, comfortably placing HTHH in the "megatsunami" league. We present a tsunami simulation of the Tongan Archipelago calibrated by field observations, drone, and satellite data.

Functional Aspects of Sperm Chromatin Organization.

Sperm nuclei present a highly organized and condensed chromatin due to the interchange of histones by protamines during spermiogenesis. This high DNA condensation leads to almost inert chromatin, with the impossibility of conducting gene transcription as in most other somatic cells. The major chromosomal structure responsible for DNA condensation is the formation of protamine-DNA toroids containing 25-50 kilobases of DNA.

Determination of double- and single-stranded DNA breaks in bovine sperm is predictive of their fertilizing capacity.

Background: The analysis of chromatin integrity has become an important determinant of sperm quality. In frozen-thawed bovine sperm, neither the sequence of post-thaw injury events nor the dynamics of different types of sperm DNA breaks are well understood. The aim of the present work was to describe such sperm degradation aftermath focusing on DNA damage dynamics, and to assess if this parameter can predict pregnancy rates in cattle.

Sperm degradation after vasectomy follows a sperm chromatin fragmentation-dependent mechanism causing DNA breaks in the toroid linker regions.

Vasectomy is a widely used surgical technique creating an obstructive azoospermia. Although sperm cannot be ejaculated, the testis maintains sperm production in vasectomized males. The continuous accumulation of sperm deposited in the epididymis and the vas deferens fraction necessarily need to be degraded and eliminated.

Deletion of Orc4 during oogenesis severely reduces polar body extrusion and blocks zygotic DNA replication†.

Origin recognition complex subunit 4 (ORC4) is a DNA-binding protein required for DNA replication. During oocyte maturation, after the last oocyte DNA replication step and before zygotic DNA replication, the oocyte undergoes two meiotic cell divisions in which half the DNA is ejected in much smaller polar bodies. We previously demonstrated that ORC4 forms a cytoplasmic cage around the DNA that is ejected in both polar body extrusion (PBE) events.

Correction: A Neolithic Mega-Tsunami Event in the Eastern Mediterranean: Prehistoric Settlement Vulnerability Along the Carmel Coast, Israel.

[This corrects the article DOI: 10.1371/journal.pone.

A Neolithic mega-tsunami event in the eastern Mediterranean: Prehistoric settlement vulnerability along the Carmel coast, Israel.

Tsunami events in antiquity had a profound influence on coastal societies. Six thousand years of historical records and geological data show that tsunamis are a common phenomenon affecting the eastern Mediterranean coastline. However, the possible impact of older tsunamis on prehistoric societies has not been investigated.

Mechanical Ventilation of Severe Traumatic Brain Injury Patients in the Prehospital Setting.

Objective: Suboptimal ventilation may impact outcomes in patients with traumatic brain injury (TBI). This study compares the incidence of eucapnia between manually and mechanically ventilated patients with severe TBI during helicopter transport.

Methods: This retrospective chart review included consecutive intubated adults with severe TBI (Glasgow Coma Scale score < 9) transported by helicopter from the scene of injury to a level 1 trauma center between 2009 and 2015.

The role of ORC4 in enucleation of Murine Erythroleukemia (MEL) cells is similar to that in oocyte polar body extrusion.

The Origin Replication Complex subunit 4 (ORC4) is one in six subunits of the Origin Replication Complexes (ORCs) which is essential for initiating licensing at DNA replication origins and recruiting adaptor molecules necessary for various cellular processes. Previously, we reported that ORC4 also plays a vital role in polar body extrusion (PBE) during oogenesis in which half the chromosomes are extruded from the oocyte. We hypothesized that ORC4 might play a broader role in chromatin elimination.

COPD Care Bundle in Emergency Department Observation Unit Reduces Emergency Department Revisits.

Background: COPD exacerbations lead to accelerated decline in lung function, poor quality of life, and increased mortality and cost. Emergency department (ED) observation units provide short-term care to reduce hospitalizations and cost. Strategies to improve outcomes in ED observation units following COPD exacerbations are needed.

Spatial and temporal resolution of mORC4 fluorescent variants reveals structural requirements for achieving higher order self-association and pronuclei entry.

The Origin Replication Complex (ORC), which is a multi-subunit protein complex composed of six proteins ORC1-6, is essential for initiating licensing at DNA replication origins. We have previously reported that ORC4 has an alternative function wherein it forms a cage surrounding the extruded chromatin in female meiosis and is required for polar body extrusion (PBE). As this is a highly unexpected finding for protein that normally binds DNA, we tested whether ORC4 can actually form larger, higher order structures, which would be necessary to form a cage-like structure.

Higher Order Oligomerization of the Licensing ORC4 Protein Is Required for Polar Body Extrusion in Murine Meiosis.

We have previously shown that the DNA replication licensing factor ORC4 forms a cage around the chromosomes that are extruded in both polar bodies during murine oogenesis, but not around the chromosomes that are retained in the oocyte or around the sperm chromatin. We termed this structure the ORC4 cage. Here, we tested whether the formation of the ORC4 cage is necessary for polar body extrusion (PBE).

Presence of the Paternal Pronucleus Assists Embryo in Overcoming Cycloheximide Induced Abnormalities in Zygotic Mitosis.

After fertilization, the maternal and paternal chromosomes independently proceed through pronuclear formation. These chromatin reconfigurations occur within a shared cytoplasm thus exposing both gametes to the same factors. Here, we report that continuous cycloheximide [40 μg/mL] treatment of parthenogenotes, androgenotes, and ICSI embryos reveals ORC2 pronuclear instability in the maternal (MPN) but not the paternal pronucleus (PPN).

Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status.

Luminal fluid of epididymis and vas deferens contributes to sperm chromatin fragmentation.

Study Question: Do the luminal fluids of the epididymis and the vas deferens contribute to sperm chromatin fragmentation (SCF) in mice?

Summary Answer: The luminal fluids of both organs are required for activating SCF in mice, but the vas deferens luminal fluid does this more efficiently than that of the epididymis.

What Is Known Already: Mice sperm have the ability to degrade their DNA in an apoptotic-like fashion when treated with divalent cations in a process termed SCF. SCF has two steps: the induction of reversible double-strand DNA breaks at the nuclear matrix attachment sites, followed by the irreversible degradation of DNA by nuclease.

ORC proteins in the mammalian zygote.

The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins.