Safety and efficacy of inhaled IBIO123 for mild-to-moderate COVID-19: a randomised, double-blind, dose-ascending, placebo-controlled, phase 1/2 trial.

Background: COVID-19 severity is associated with its respiratory manifestations. Neutralising antibodies against SARS-CoV-2 administered systemically have shown clinical efficacy. However, immediate and direct delivery of neutralising antibodies via inhalation might provide additional respiratory clinical benefits.

Giant Hydronephrosis: A Rare Case Report and Literature Review.

Giant hydronephrosis (GH), characterized by the presence of more than 1 L of fluid in the renal collecting system, is a rare urological condition, particularly in adults. Obstruction of the pyeloureteral junction is the most common cause of GH. We report the case of a 51-year-old man who presented with dyspnea, edema of the lower limbs, and major abdominal distension.

Case Report of Bifid Ureter with a Blind Ending: Surgical Laparoscopic Management.

BACKGROUND The blind-ending branch of a bifid ureter is a rare congenital anomaly which is usually asymptomatic but can occasionally give rise to various symptoms, such as chronic abdominal pain. Diagnosis is most often confirmed radiologically, and treatment is usually conservative. Surgical resection of the blind ending of a bifid ureter should be considered in cases of persistent symptoms.

The DNA double-strand "breakome" of mouse spermatids.

De novo germline mutations arise preferentially in male owing to fundamental differences between spermatogenesis and oogenesis. Post-meiotic chromatin remodeling in spermatids results in the elimination of most of the nucleosomal supercoiling and is characterized by transient DNA fragmentation. Using three alternative methods, DNA from sorted populations of mouse spermatids was used to confirm that double-strand breaks (DSB) are created in elongating spermatids and repaired at later steps.

Quantification and genome-wide mapping of DNA double-strand breaks.

DNA double-strand breaks (DSBs) represent a major threat to the genetic integrity of the cell. Knowing both their genome-wide distribution and number is important for a better assessment of genotoxicity at a molecular level. Available methods may have underestimated the extent of DSBs as they are based on markers specific to those undergoing active repair or may not be adapted for the large diversity of naturally occurring DNA ends.

Step-specific Sorting of Mouse Spermatids by Flow Cytometry.

The differentiation of mouse spermatids is one critical process for the production of a functional male gamete with an intact genome to be transmitted to the next generation. So far, molecular studies of this morphological transition have been hampered by the lack of a method allowing adequate separation of these important steps of spermatid differentiation for subsequent analyses. Earlier attempts at proper gating of these cells using flow cytometry may have been difficult because of a peculiar increase in DNA fluorescence in spermatids undergoing chromatin remodeling.

Immuno-capture of UVDE generated 3'-OH ends at UV photoproducts.

A strategy amenable to the genome-wide study of DNA damage and repair kinetics is described. The ultraviolet damage endonuclease (UVDE) generates 3'-OH ends at the two major UV induced DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6,4 pyrimidine-pyrimidone dimers (6,4 PPs), allowing for their capture after biotin end-labeling. qPCR amplification of biotinylated DNA enables parallel measuring of DNA damage in several loci, which can then be combined with high-throughput screening of cell survival to test genotoxic reagents.

Instability of trinucleotidic repeats during chromatin remodeling in spermatids.

Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.

Male-driven de novo mutations in haploid germ cells.

At the sequence level, genetic diversity is provided by de novo transmittable mutations that may act as a substrate for natural selection. The gametogenesis process itself is considered more likely to induce endogenous mutations and a clear male bias has been demonstrated from recent next-generation sequencing analyses. As new experimental evidence accumulates, the post-meiotic events of the male gametogenesis (spermiogenesis) appear as an ideal context to induce de novo genetic polymorphism transmittable to the next generation.

Genome-wide mapping of DNA strand breaks.

Determination of cellular DNA damage has so far been limited to global assessment of genome integrity whereas nucleotide-level mapping has been restricted to specific loci by the use of specific primers. Therefore, only limited DNA sequences can be studied and novel regions of genomic instability can hardly be discovered. Using a well-characterized yeast model, we describe a straightforward strategy to map genome-wide DNA strand breaks without compromising nucleotide-level resolution.

The sperm nucleus: chromatin, RNA, and the nuclear matrix.

Within the sperm nucleus, the paternal genome remains functionally inert and protected following protamination. This is marked by a structural morphogenesis that is heralded by a striking reduction in nuclear volume. Despite these changes, both human and mouse spermatozoa maintain low levels of nucleosomes that appear non-randomly distributed throughout the genome.

A large ribonucleoprotein particle induced by cytoplasmic PrP shares striking similarities with the chromatoid body, an RNA granule predicted to function in posttranscriptional gene regulation.

The observation that PrP is present in the cytosol of some neurons and non-neuronal cells and that the N-terminal signal peptide is slightly inefficient has brought speculations concerning a possible function of the protein in the cytosol. Here, we show that cells expressing a cytosolic form of PrP termed cyPrP display a large juxtanuclear cytoplasmic RNA organelle. Although cyPrP spontaneously forms aggresomes, we used several mutants to demonstrate that the assembly of this RNA organelle is independent from cyPrP aggregation.

Spermiogenesis and DNA repair: a possible etiology of human infertility and genetic disorders.

This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids.

DNA damage response during chromatin remodeling in elongating spermatids of mice.

A precise packaging of the paternal genome during spermiogenesis is essential for fertilization and embryogenesis. Most of the nucleosomal DNA supercoiling must be eliminated in elongating spermatids (ES), and transient DNA strand breaks are observed that facilitate the process. Topoisomerases have been considered as ideal candidates for the removal of DNA supercoiling, but their catalytic activity, in the context of such a major chromatin remodeling, entails genetic risks.

Growth and reproduction of the earthworm Eisenia fetida after exposure to leachate from wood preservatives.

Wood preserved with chromated copper arsenate (CCA) and alkaline copper quaternary (ACQ) was mixed with artificial rainwater, to generate leachates containing As, Cr and Cu. Then, leachates were applied to two soils at rates of 13-169 mg As kg(-1) soil (dry weight basis), 12-151 mg Cr kg(-1) and 10-216 mg Cu kg(-1). Metal bioavailability was evaluated after 28 days using the earthworm Eisenia fetida (Savigny).

Laparoscopic resection of a leiomyoma of the seminal vesicle.

We present a case of a leiomyoma of the seminal vesicle that occurred in a 52-year-old man who presented with symptoms of bladder outlet obstruction. Prostate-specific antigen was within normal limit. Computed tomography scan and magnetic resonance imaging revealed a mass in the patient's right seminal vesicle.