Parkinson's disease plasma biomarkers: An automated literature analysis followed by experimental validation

Diagnosis of Parkinson's disease (PD) is currently assessed by the clinical evaluation of extrapyramidal signs. The identification of specific biomarkers would be advisable, however most studies stop at the discovery phase, with no biomarkers reaching clinical exploitation. To this purpose, we developed an automated literature analysis procedure to retrieve all the background knowledge available in public databases. The bioinformatic platform allowed us to analyze more than 51,000 scientific papers dealing with PD, containing information on 4121 proteins. Out of these, we could track back 35 PD-related proteins as present in at least two published 2-DE maps of human plasma. Then, 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen γ, thrombin, complement C3) split into 32 spots were identified as a potential diagnostic pattern. Eventually, we compared the collected literature data to experimental gels from 90 subjects (45 PD patients, 45 non-neurodegenerative control subjects) to experimentally verify their potential as plasma biomarkers of PD

Rapid malignant progression of an intraparenchymal choroid plexus papillomas

Background: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. Case Description: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. Conclusion: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location

Peripheral facial palsy following ventriculoperitoneal shunt. The lesson we have learned

The most frequent complications after shunt surgery are infective and obstructive. Other types are less common, and eventually occur due to technical errors during brain ventricular puncture, opening the intraperitoneal cavity or the tunnelling of the catheter between the two points. Although rare, there are well-reported complications related to the poor positioning of the distal catheter, with perforation of organs and tissues. We report a very rare case of a male patient with normal pressure hydrocephalus submitted to ventriculoperitoneal shunt. During tunnelling of the shunt stylet, a peripheral facial palsy due to injury to the extra cranial segment of the facial nerve occurred. To the best of our knowledge this is the second case described in Literature. The patient and the surgeon should be aware of this very rare but possible complication in shunt surgery being careful to the course of the facial nerve in the mastoid region

Axolotl Nanog activity in mouse embryonic stem cells demonstrates that ground state pluripotency is conserved from urodele amphibians to mammals

Cells in the pluripotent ground state can give rise to somatic cells and germ cells, and the acquisition of pluripotency is dependent on the expression of Nanog. Pluripotency is conserved in the primitive ectoderm of embryos from mammals and urodele amphibians, and here we report the isolation of a Nanog ortholog from axolotls (axNanog). axNanog does not contain a tryptophan repeat domain and is expressed as a monomer in the axolotl animal cap. The monomeric form is sufficient to regulate pluripotency in mouse embryonic stem cells, but axNanog dimers are required to rescue LIF-independent self-renewal. Our results show that protein interactions mediated by Nanog dimerization promote proliferation. More importantly, they demonstrate that the mechanisms governing pluripotency are conserved from urodele amphibians to mammals. © 2010. Published by The Company of Biologists Ltd

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach

Combined use oíreduced doses oíFSH-P and eCG as superovulatory treatment in cattle

Para evaluarla respuesta ovárica después de administrar dosis reducidas de: FSH-P, eCG o su combinación, se utilizaron 12 vacas y 24 vaquillonas (Angus, condición corporal: 6,9±0,1; x±e.e.; escala 1 a 9). Se distribuyeron aleatoriamente en tres grupos: ½FSH-P: FSH-P, 5 ó 6 mg Armour vía intramuscular (IM) y 10 u 11 mg vía subcutánea (SC) en vaquillonas y vacas, respectivamente, administrados en dosis única y simultánea. ½eCG: 1000 o 1250 UI de eCG, SC, en vaquillonas y vacas, respectivamente. FSH-P + eCG: Vaquillonas: 5 mg de FSH-P, IM, y al mismo tiempo, 1000 UI de eCG y 10 mg de FSH-P, SC. Vacas: Ídem vaquillonas con: 6 mg, 1250 UI y 11 mg, respectivamente. Se inyectó Cloprostenol a las 48 h (500 μg) y 60 h (250 μg) de comenzado el tratamiento superovulatorio [día 10,0±0,1 (x±ee) del ciclo estral]. Se inseminaron a las 60 y 72 h post Cloprostenol con semen congelado/descongelado. Siete días después se recolectaron los ovocitos/embriones. El análisis estadístico se realizó utilizando el SAS. No se observaron efectos de la categoría de animal. La respuesta superovulatoria (p<0,01) fue superior en FSH-P + eCG (100%) comparada con ½FSH-P (6,25%) y ½eCG (25%). El número de CL, embriones totales, transferiblesy congelables fue superior en FSH-P + eCG (p< 0,01); %FSH- P y %eCG no difiriendo entre sí (CL: 7,6±0,8; 1,3±0,2; 1,9±0,4; Embriones totales: 6,3±0,7; 0,06±0,06; 0,7±0,4; transferibles: 4,3±0,5; 0,06±0,06; 0,3±0,2; congelables: 3,0±0,4; 0; 0,06±0,l; x±ee; FSH-P + eCG; ½FSH-P y ½eCG, respectivamente). La presencia de un folículo dominante en crecimiento y la concentración de progesterona afectaron la respuesta superovulatoria. En conclusión, las dosis reducidas utilizadas de FSH-P o de eCG son insuficientes para producir una respuesta ovárica compatible con tratamientos superovulatorios convencionales. La presencia de un folículo dominante en crecimiento y la concentración de progesterona al inicio del tratamiento superovulatorio afectan la respuesta al mismo.To evaluated the ovarian response after administration of reduced doses of FSH-P, eCG or a combination ofboth, 12 cows and 24 heifers (Angus, body condition: 6.9 ±0.1; x±s.d.; scale 1 to 9) were assigned to three treatments: ½FSH-P: FSH-P, 5 or 6 mg Armour intramuscularly (IM) and 10 or 11 mg subcutaneously (SC) in heifers and cows, respectively, administered as a sole and simultaneous dose. ½eCG, 1000 or 1250 UI of eCG were SC administered to heifers and cows, respectively. FSH-P + eCG, heifers: 5 mg FSH-P and, at the same time, 1000 UI eCG + 10 mg FSH-P, SC. The same administration scheme was used for cows with: 6 mg, 1250 UI and 11 mg, respectively. All the animals were injected Cloprostenol at 48 h (500 μg) and 60 h (250 μg) after the beginning superovulatory treatment [day 10.0±0.1 (x±sd) of the estrous cycle]. The animals were inseminated at 60 and 72 h post Cloprostenol with frozen semen. After seven days, oocytes/embryos were collected. Statistical analyses were performed by SAS. No animal category effect was observed. The superovulatory response were greater in the FSH-P + eCG (100%) (p<0.01) than ½FSH-P (6.25%) and ½eCG (25%). The number of CL, total embryos, transferable and freezable from FSH-P + eCG was greater (p<0.01) than ½FSH-P and ½eCG; no difference was observed between the latter (CL: 7.6±0.8; 1.3±0.2; 1.9±0.4; total embryos: 6.3±0.7; 0.06±0.06; 0.7±0.4; transferable: 4.3±0.5; 0.06±0.06; 0.3±0.2; freezable: 3.0±0.4; 0; 0.06 ±0.1; x±sd; FSH-P + eCG; ½FSH-P and ½eCG, respectively). The presence of a growing dominant follicle and progesterone concentration at the beginning of the superovulatory treatment affected negatively treatment response. It is concluded that reduced doses of FSH- P or eCG utilized are insufficient to produce an ovarian response compatible with those of conventional superovulatory treatments. The presence of a growing dominant follicle and the progesterone concentration at the beginning of treatment affect the superovulatory response.Facultad de Ciencias Veterinaria

Epigenetic reprogramming of breast cancer cells with oocyte extracts

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.</p> <p>Results</p> <p>We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.</p> <p>Conclusions</p> <p>This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.</p

Principles of early human development and germ cell program from observed model systems

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during weeks 2–3 of early post-implantation development$^{1}$. Using $\textit{in vitro}$ models of hPGC induction$^{2, 3, 4}$, recent studies have suggested that there are marked mechanistic differences in the specification of human and mouse PGCs$^{5}$. This may be due in part to the divergence in their pluripotency networks and early post-implantation development$^{6, 7, 8}$. As early human embryos are not accessible for direct study, we considered alternatives including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs originate from the posterior pre-primitive-streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. We use this model together with human and monkey $\textit{in vitro}$ models simulating peri-gastrulation development to show the conserved principles of epiblast development for competency for primordial germ cell fate. This process is followed by initiation of the epigenetic program$^{9, 10, 11}$ and regulated by a balanced $\textit{SOX17–BLIMP1}$ gene dosage. Our combinatorial approach using human, porcine and monkey $\textit{in vivo}$ and $\textit{in vitro}$ models provides synthetic insights into early human development.Wellcome Trust Medical Research Council BBSR