CCN6 Suppresses Metaplastic Breast Carcinoma by Antagonizing Wnt/β-Catenin Signaling to Inhibit EZH2-Driven EMT.

Metaplastic breast carcinomas (mBrCA) are a highly aggressive subtype of triple-negative breast cancer with histologic evidence of epithelial-to-mesenchymal transition and aberrant differentiation. Inactivation of the tumor suppressor gene cellular communication network factor 6 (CCN6; also known as Wnt1-induced secreted protein 3) is a feature of mBrCAs, and mice with conditional inactivation of Ccn6 in mammary epithelium (Ccn6-KO) develop spindle mBrCAs with epithelial-to-mesenchymal transition. Elucidation of the precise mechanistic details of how CCN6 acts as a tumor suppressor in mBrCA could help identify improved treatment strategies.

Production of light-coloured, low heat-absorbing Holstein Friesian cattle by precise embryo-mediated genome editing.

Context: Genome editing enables the introduction of beneficial sequence variants into the genomes of animals with high genetic merit in a single generation. This can be achieved by introducing variants into primary cells followed by producing a live animal from these cells by somatic cell nuclear transfer cloning. The latter step is associated with low efficiencies and developmental problems due to incorrect reprogramming of the donor cells, causing animal welfare concerns.

Cytoplasmic Injection of Zygotes to Genome Edit Naturally Occurring Sequence Variants Into Bovine Embryos.

Genome editing provides opportunities to improve current cattle breeding strategies through targeted introduction of natural sequence variants, accelerating genetic gain. This can be achieved by harnessing homology-directed repair mechanisms following editor-induced cleavage of the genome in the presence of a repair template. Introducing the genome editors into zygotes and editing in embryos has the advantage of uncompromised development into live animals and alignment with contemporary embryo-based improvement practices.

Holstein Friesian dairy cattle edited for diluted coat color as a potential adaptation to climate change.

Background: High-producing Holstein Friesian dairy cattle have a characteristic black and white coat, often with large proportions of black. Compared to a light coat color, black absorbs more solar radiation which is a contributing factor to heat stress in cattle. To better adapt dairy cattle to rapidly warming climates, we aimed to lighten their coat color by genome editing.

The genomes of precision edited cloned calves show no evidence for off-target events or increased de novo mutagenesis.

Background: Animal health and welfare are at the forefront of public concern and the agricultural sector is responding by prioritising the selection of welfare-relevant traits in their breeding schemes. In some cases, welfare-enhancing traits such as horn-status (i.e.

Striking heterogeneity of somatic L1 retrotransposition in single normal and cancerous gastrointestinal cells.

Somatic LINE-1 (L1) retrotransposition has been detected in early embryos, adult brains, and the gastrointestinal (GI) tract, and many cancers, including epithelial GI tumors. We previously found numerous somatic L1 insertions in paired normal and GI cancerous tissues. Here, using a modified method of single-cell analysis for somatic L1 insertions, we studied adenocarcinomas of colon, pancreas, and stomach, and found a variable number of somatic L1 insertions in tumors of the same type from patient to patient.

Transgenic goats producing an improved version of cetuximab in milk.

Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs.

Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen beta-lactoglobulin.

We applied precise  zygote-mediated genome editing to eliminate beta-lactoglobulin (BLG), a major allergen in cows' milk. To efficiently generate LGB knockout cows, biopsied embryos were screened to transfer only appropriately modified embryos. Transfer of 13 pre-selected embryos into surrogate cows resulted in the birth of three calves, one dying shortly after birth.

Increased gene dosage for β- and κ-casein in transgenic cattle improves milk composition through complex effects.

We have previously generated transgenic cattle with additional copies of bovine β- and κ casein genes. An initial characterisation of milk produced with a hormonally induced lactation from these transgenic cows showed an altered milk composition with elevated β-casein levels and twofold increased κ-casein content. Here we report the first in-depth characterisation of the composition of the enriched casein milk that was produced through a natural lactation.

Healed Depressed Parasagittal Skull Fractures-A Feature of Archaic Australian Aboriginal Remains.

The skeletal remains of eight Australian Aboriginals with healed depressed skull fractures were examined. Male:female ratio 5:3; age range 20-60 yrs. Burial dates by C dating in three cases were 500 years BP (n = 2) and 1300 BP.

Cranio-cervical decompression and expansile duroplasty for isolated fourth ventricle in a patient with Chiari II malformation.

The management of isolated fourth ventricle in Chiari II malformation remains a complex challenge. Commonly accepted treatment options have been associated with high rates of complications and failure. Cranio-cervical decompression and autologous expansile duroplasty may be an effective primary intervention for this condition.

A surgical model of permanent and transient middle cerebral artery stroke in the sheep.

Background: Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA) ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion.

Endoscopic endonasal resection of anterior skull base meningiomas.

Objective: Anterior cranial fossa (ACF) meningiomas are difficult to surgically manage. Endoscopic transnasal approaches have increasingly been used as a minimally invasive route and thus offer significant advantages. However, a paucity of literature describing the intraoperative challenges and postoperative outcomes of this technique still exists.

Hyperprolactinaemia and the empty sella.

Hyperprolactinaemia is an endocrine abnormality seen not infrequently in the population with empty sella; a radiological and anatomical diagnosis of a deformed and enlarged sella turcica. Often there is no associated pathology within the pituitary gland itself, lending to the hypothesis that the empty sella syndrome per se has a yet-to-be defined role in hyperprolactinemia. We report a patient who presented initially with non-specific symptoms of meningeal irritation and viral illness on a long background of galactorrhoea.

Practical neurology - 3: Back pain and leg weakness.

Back pain is very common; it has a point prevalence of 25% and is the third most common reason for consultation in Australian general practice. A thorough history and examination can identify the minority of patients who require urgent neuroimaging or other targeted investigations. Careful correlation of clinical and radiological findings is required when abnormal neurological findings are detected.

Neuro-ophthalmic manifestations and outcomes of pituitary apoplexy--a life and sight-threatening emergency.

Objective: To report the neuro-ophthalmic manifestations and outcomes in patients with pituitary apoplexy.

Method: Retrospective chart review.

Results: 23 patients were identified (17 men, mean age 54.

Subarachnoid haemorrhage in a patient with a left temporal arteriovenous malformation and an associated anterior communicating artery aneurysm.

We report a patient who presented with a subarachnoid haemorrhage in the setting of both an arteriovenous malformation and an intracerebral aneurysm. It was felt that the aneurysm had bled and both abnormalities were treated surgically in a sequential manner. The problem of aneurysm combined with arteriovenous malformation is reviewed.

Stereotactic radiosurgery for acoustic neuromas: what happens long term?

Purpose: To determine the clinical outcomes for acoustic neuroma treated with low-dose linear accelerator stereotactic radiosurgery (SRS) >10 years earlier at the Royal Adelaide Hospital using data collected prospectively at a dedicated SRS clinic.

Methods And Materials: Between November 1993 and December 2000, 51 patients underwent SRS for acoustic neuroma. For the 44 patients with primary SRS for sporadic (unilateral) lesions, the median age was 63 years, the median of the maximal tumor diameter was 21 mm (range, 11-34), and the marginal dose was 14 Gy for the first 4 patients and 12 Gy for the other 40.

Lessons from a 17-year radiosurgery experience at the Royal Adelaide Hospital.

Purpose: To illustrate some of the potential pitfalls of cranial stereotactic radiosurgery (SRS) and its planning based on prospectively gathered data from a 17-year experience at the Royal Adelaide Hospital.

Methods And Materials: More than 250 treatments have been planned since 1993 using previously described standard SRS techniques for intracranial benign and malignant lesions.

Results: Five case studies are presented (1 meningioma, 1 acoustic neuroma, 2 solitary brain metastasis, 1 arteriovenous malformation), each of which demonstrates at least one salutary lesson.

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson's disease.

Motor cortex excitability was assessed in 12 patients with Parkinson's disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated ("ON") and when immobile after medication withdrawal ("OFF"). Results were compared to eight age-matched and 11 young controls.

Blister-like aneurysm of the anterior communicating artery.

We report a recent experience with a blister-like aneurysm of the anterior communicating artery and suggest that this entity may be responsible for so-called non-aneurysmal haemorrhage when the distribution of blood is atypical.

On-line casein micelle disruption for downstream purification of recombinant human myelin basic protein produced in the milk of transgenic cows.

Downstream purification of a model recombinant protein (human myelin basic protein) from milk of transgenic cows is described. The recombinant protein was expressed as a His tagged fusion protein in the milk of transgenic cows and was found associated with the casein micellar phase. While difficulties in obtaining good recoveries were found when employing conventional micelle disruption procedures, direct capture using the cation exchanger SP Sepharose Big Beads was found successful in the extraction of the recombinant protein.

Posterior projecting carotid bifurcation aneurysms.

Posteriorly projecting carotid bifurcation aneurysms are rare. Proximal anterior cerebral artery aneurysms are even more uncommon. Distinguishing between true posteriorly projecting carotid bifurcation aneurysms and carotid A1 aneurysms can be difficult but it is important because small posteriorly projecting carotid bifurcation aneurysms may need a contralateral approach for adequate exposure.