Ophthalmic Segment Aneurysms: Surgical Treatment and Outcomes

Background Surgical treatment of ophthalmic segment aneurysms (OSAs) remain challenging because of complex anatomy surrounding the aneurysm and entails extensive drilling of anterior clinoid process to define proximal neck of the aneurysm and carotid exposure in the neck for proximal control. Materials and Methods Authors present a retrospective analysis of 36 aneurysms in 35 patients with OSAs operated surgically by first author. Surgical clipping was done for the aneurysms as primary modality of treatment along with wrapping and trapping as required. Results Commonest age group was 40 to 60 years with female preponderance of 3:1. Maximum (23) patients presented with subarachnoid hemorrhage (WFNS Gr 1), followed by asymptomatic patients (six). There were 18 small, 14 large, and four giant aneurysms, 15 dorsal wall, 17 ventral wall, three proximal posterior wall, and one blister aneurysm. Good outcome, as measured by Glasgow Outcome Score (GOS) was achieved in 29 patients. Conclusion OSAs are technically demanding aneurysms, but with due diligence to surgical principles, good outcomes may be obtained.

Identification of the cell-type-specific ER membrane protein Tanmp expressed in hypothalamic tanycytes and subsets of neurons

Genomes of higher eukaryotes encode many uncharacterized proteins, and the functions of these proteins cannot be predicted from the primary sequences due to a lack of conserved functional domains. During a screening of novel noncoding RNAs abundantly expressed in mouse brains, we incidentally identified a gene termed Tanmp, which encoded an endoplasmic reticulum (ER) protein without known functional domains. Tanmp is specifically expressed in the nervous system, and the highest expression was observed in a specialized cell type called tanycyte that aligns the ventral wall of the third ventricle in the hypothalamus. Immunostaining of Tanmp revealed the fine morphology of tanycytes with highly branched apical ER membranes. Immunoprecipitation revealed that Tanmp associates with mitochondrial ATPase at least in vitro, and ER and mitochondrial signals occasionally overlapped in tanycytes. Mutant mice lacking Tanmp did not exhibit overt phenotypes, suggesting that Tanmp is not essential in mice reared under normal laboratory conditions. We also found that RNA probes that are predicted to uniquely detect Tanmp mRNA cross-reacted with uncharacterized RNAs, highlighting the importance of experimental validation of the specificity of probes during the hybridization-based study of RNA localization.

The Fgf8 subfamily (Fgf8, Fgf17 and Fgf18) is required for closure of the embryonic ventral body wall

ABSTRACTThe closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are extruded. By refining where and when these genes are required using different Cre lines, we show that Fgf8 and Fgf17 are required in the presomitic mesoderm, whereas Fgf18 is required in the somites. This study identifies complex and multifactorial origins of ventral wall defects and has important implications for understanding their origins during embryonic development.

Origin and role of the cerebrospinal fluid bidirectional flow in the central canal

Circulation of the cerebrospinal fluid (CSF) contributes to body axis formation and brain development. Here, we investigated the unexplained origins of the CSF flow bidirectionality in the central canal of the spinal cord of 30 hpf zebrafish embryos and its impact on development. Experiments combined with modeling and simulations demonstrate that the CSF flow is generated locally by caudally-polarized motile cilia along the ventral wall of the central canal. The closed geometry of the canal imposes the average flow rate to be null, explaining the reported bidirectionality. We also demonstrate that at this early stage, motile cilia ensure the proper formation of the central canal. Furthermore, we demonstrate that the bidirectional flow accelerates the transport of particles in the CSF via a coupled convective-diffusive transport process. Our study demonstrates that cilia activity combined with muscle contractions sustain the long-range transport of extracellular lipidic particles, enabling embryonic growth.

Hypospadias in a Sheltie puppy: A case report

Hypospadias in dogs is a rare pathology in the veterinary practice. The manifestation of hypospadias in dogs is diverse, since there is a varying degree of damage to the urogenital apparatus. The owners of a Sheltie puppy at the age of 3 days came to the clinic due to the difficulty of determining sex, the presence of inflammation of the anus and abdominal skin, defecation and urination violations. Clinical examination of the puppy showed a blind-closed preputial sac, absence of the ventral wall of the prepuce and an open urogenital urine trough was located in its place in the abdominal wall area. On examination of the puppy at the age of 28 days, hyperaemia and swelling of the anus were noted, as well as prolapse of the rectum. Findings of the examination at the age of 4 months consisted of drying of the mucous part of the open urogenital canal chute and accumulation of pus in the underdeveloped preputial sac. Bilateral cryptorchidism and the absence of the scrotum were also found out. A decision on the surgical treatment was made. The anus and the opening of the urethra were separated to form a urethrostomy in the scrotum and restore the integrity of the anus. On the 5th post operative day, oedema and stricture of the reconstructed urethra resulted in difficulty urinating, followed by the formation of urinary fistula in the perineal region below the anus opening. As a result of the chosen surgical treatment approach, the problem with contact dermatitis of the perineum and pollakiuria was solved.

Pulsation Activates Mechanosensitive Piezo1 to Form Long-Term Hematopoietic Stem Cells

The temporal and spatial origin and development of long-term, self-renewing hematopoietic stem cells (LT-HSC) remain a mystery. The first set of definitive HSCs is born from the hemogenic endothelial cells residing in the ventral wall of the dorsal aorta (DA) of the aorta-gonad-mesonephros region during embryonic development. Blood flow- and shear-stress-mediated nitric oxide-induced vasodilation are responsible for the endothelial-to-HSC transition (EHT). However, it remains unknown why the ventral wall, and not the dorsal wall, of the DA is the restricted site of the EHT when blood flows through the entire DA and exerts shear stress on both the ventral and dorsal sides of the DA. Using single-particle tracking and fast Fourier Transform analyses of pulsating blood vessels, we demonstrate that the circumferential strain in the ventral wall, and not dorsal wall, is concurrent with and responsible for the magnitude, the site, and timing of the HSC formation. We extended our findings by developing a bioreactor to establish the functional link between pulsation in the blood vessels and HSC formation. Using serial transplant, limiting dilution, and serial replating assays, we found that pulsation mediated circumferential stretching of hemogenic endothelial cells or Piezo1 activation (Yoda1) yields 3-times higher amounts of Long Term (LT)-HSC formation; which reconstitute to normal multi-lineage adult blood. Using delayed-type hypersensitivity assay, adult globin expression, MPO enzyme activity, immunoglobulins, and T-cell receptor rearrangement analyses, we found that circumferential stretching or Piezo1 activation-derived HSCs reconstitute to functional T and B cells, adult erythrocytes, and myeloid cells. Our Piezo1fl/flxScl-Cre conditional knockout, gene-silencing, & confocal imaging further demonstrate that circumferential stretching of blood vessels activates Piezo1; which enhances epigenetic regulator Dnmt3b expression to stimulate the EHT. Our CUT&RUN CHIP-Sequencing & MASSArray methylation analyses demonstrate that Dnmt3b suppresses endothelial genes during EHT. To analyze the conserved role of PIEZO1-mediated mechanosensitive mechanisms in human hematopoiesis, we employed directed differentiation of constitutive RUNX1-mCherry human induced pluripotent stem cells (iPSCs) to hemogenic endothelial cells. We found that Yoda1-mediated PIEZO1 activation stimulated human endothelial-to-hematopoietic transition. In conclusion, pulsation-mediated circumferential strain activates Piezo1 to stimulate the endothelial-to-HSC transition via the induction of Dnmt3b expression. This leads to the formation of long-term self-renewing HSCs, which can engraft and reconstitute to multi-lineage, adult blood upon serial transplantations. Our identification of a novel biomechanical cue unravels the physiological mystery in HSC formation in the ventral wall of the DA. We also establish its cross-talk with mechanosensitive and epigenetic mechanisms to produce functional, long-term HSCs that reconstitute to form normal adult blood. This yields the therapeutic promise of developing transgene-free LT-HSC-based cellular therapies for the treatment of human blood disorders. Disclosures No relevant conflicts of interest to declare.

Corrigenda to Gil-Santana, H.R. 2018. A new species of Phasmatocoris from French Guiana, with short taxonomic notes on two described species and an updated key (Hemiptera: Heteroptera: Reduviidae: Emesinae). Zootaxa 4413 (3): 491–506

An intraspecific variation of the male genitalia of Phasmatocoris papei Gil-Santana, 2018 (Hemiptera: Heteroptera: Reduviidae: Emesinae: Emesini), i.e., the absence (holotype) / presence (paratype) of the sclerotization of approximately basal two thirds of the ventral wall of phallosoma, reported by Gil-Santana (2018), was found to be incorrect. A subsequent reexamination of the specimens revealed that the misjudgement was based on a breakage of this structure in the phallus of the holotype. In fact, the ventral wall of phallosoma was completely sclerotized at its basal two-thirds in both specimens and should be considered as a species level character of Ph. papei.