Generation of human iPSC-derived phrenic-like motor neurons to model respiratory motor neuron degeneration in ALS.

The fatal motor neuron (MN) disease Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive MN degeneration. Phrenic MNs (phMNs) controlling the activity of the diaphragm are prone to degeneration in ALS, leading to death by respiratory failure. Understanding of the mechanisms of phMN degeneration in ALS is limited, mainly because human experimental models to study phMNs are lacking.

Response to Comment on "Pushing the frontiers of density functionals by solving the fractional electron problem".

Gerasimov . claim that the ability of DM21 to respect fractional charge (FC) and fractional spin (FS) conditions outside of the training set has not been demonstrated in our paper. This is based on (i) asserting that the training set has a ~50% overlap with our bond-breaking benchmark (BBB) and (ii) questioning the validity and accuracy of our other generalization examples.

Heterozygous Mutant Mice Have a Subtle Locomotor Phenotype.

Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic mutations, while heterozygous mutants have not been closely examined.

Optimization of Long-Term Human iPSC-Derived Spinal Motor Neuron Culture Using a Dendritic Polyglycerol Amine-Based Substrate.

Human induced pluripotent stem cells (hiPSCs) derived from healthy and diseased individuals can give rise to many cell types, facilitating the study of mechanisms of development, human disease modeling, and early drug target validation. In this context, experimental model systems based on hiPSC-derived motor neurons (MNs) have been used to study MN diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. Modeling MN disease using hiPSC-based approaches requires culture conditions that can recapitulate in a dish the events underlying differentiation, maturation, aging, and death of MNs.

Pushing the frontiers of density functionals by solving the fractional electron problem.

Density functional theory describes matter at the quantum level, but all popular approximations suffer from systematic errors that arise from the violation of mathematical properties of the exact functional. We overcame this fundamental limitation by training a neural network on molecular data and on fictitious systems with fractional charge and spin. The resulting functional, DM21 (DeepMind 21), correctly describes typical examples of artificial charge delocalization and strong correlation and performs better than traditional functionals on thorough benchmarks for main-group atoms and molecules.

Characterization of Human iPSC-derived Spinal Motor Neurons by Single-cell RNA Sequencing.

Human induced pluripotent stem cells (iPSCs) offer the opportunity to generate specific cell types from healthy and diseased individuals, allowing the study of mechanisms of early human development, modelling a variety of human diseases, and facilitating the development of new therapeutics. Human iPSC-based applications are often limited by the variability among iPSC lines originating from a single donor, as well as the heterogeneity among specific cell types that can be derived from iPSCs. The ability to deeply phenotype different iPSC-derived cell types is therefore of primary importance to the successful and informative application of this technology.

Solid harmonic wavelet scattering for predictions of molecule properties.

We present a machine learning algorithm for the prediction of molecule properties inspired by ideas from density functional theory (DFT). Using Gaussian-type orbital functions, we create surrogate electronic densities of the molecule from which we compute invariant "solid harmonic scattering coefficients" that account for different types of interactions at different scales. Multilinear regressions of various physical properties of molecules are computed from these invariant coefficients.

DSCAM Mutation Impairs Motor Cortex Network Dynamic and Voluntary Motor Functions.

While it is well known that netrin-1 and its receptors UNC5 and UNC40 family members are involved in the normal establishment of the motor cortex and its corticospinal tract, less is known about its other receptor Down syndrome cell adherence molecule (DSCAM). DSCAM is expressed in the developing motor cortex, regulates axonal outgrowth of cortical neurons, and its mutation impairs the dendritic arborization of cortical neurons, thus suggesting that it might be involved in the normal development and functioning of the motor cortex. In comparison to WT littermates, DSCAM2J mutant mice slipped and misplaced their paw while walking on the rungs of a horizontal ladder, and exhibited more difficulties in stepping over an obstacle while walking at slow speed.

Age- and speed-dependent modulation of gaits in DSCAM mutant mice.

Gaits depend on the interplay between distributed spinal neural networks, termed central pattern generators, generating rhythmic and coordinated movements, primary afferents, and descending supraspinal inputs. Recent studies demonstrated that the mouse displays a rich repertoire of gaits. Changes in gaits occur in mutant mice lacking particular neurons or molecular signaling pathways implicated in the normal establishment of these neural networks.

Betacellulin regulates schwann cell proliferation and myelin formation in the injured mouse peripheral nerve.

When a nerve fiber is cut or crushed, the axon segment that is separated from the soma degenerates distal from the injury in a process termed Wallerian degeneration (WD). C57BL/6OlaHsd-Wld (Wld ) mutant mice exhibit significant delays in WD. This results in considerably delayed Schwann cell and macrophage responses and thus in impaired nerve regenerations.

Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth.

Role of DSCAM in the development of the spinal locomotor and sensorimotor circuits.

Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance.

A root chicory MADS box sequence and the Arabidopsis flowering repressor FLC share common features that suggest conserved function in vernalization and de-vernalization responses.

Root chicory (Cichorium intybus var. sativum) is a biennial crop, but is harvested to obtain root inulin at the end of the first growing season before flowering. However, cold temperatures may vernalize seeds or plantlets, leading to incidental early flowering, and hence understanding the molecular basis of vernalization is important.

Daily burdens of recipients and family caregivers after lung transplant.

Context: Lung transplant recipients are prescribed a complex medical regimen that is thought to be burdensome and to interfere with daily activities of recipients and family caregivers. Yet empirical studies describing the activities that lung transplant recipients and their family caregivers perform on a typical day and the emotions associated with performing these activities are lacking.

Objective: To identify the daily activities and burdens after lung transplant.

Human recombinant myeloperoxidase antiviral activity on cytomegalovirus.

In vitro incubation of human cytomegalovirus (Towne strain) with 8 U/ml human recombinant myeloperoxidase plus sodium chloride and glucose nearly abolished viral infectivity. To assay the effect on intracellular infection, cell toxicity of the enzymes was first studied. Even the high dose of 16 U/ml of recombinant myeloperoxidase plus 10 mU/ml glucose oxidase did not decrease MRC5 cell growth.

A human milk factor susceptible to cathepsin D inhibitors enhances human immunodeficiency virus type 1 infectivity and allows virus entry into a mammary epithelial cell line.

Human immunodeficiency virus type 1 (HIV-1) growth in lymphocyte cultures was increased when the virus inoculum was incubated in breast milk. The enhancing effect of milk was abolished by anti-cathepsin D antibody or by pepstatin A, a cathepsin D inhibitor. The cathepsin D-producing CD4-negative MCF7 mammary cells supported the growth of some HIV-1 isolates.

Management of common bile duct stones in a single operation combining laparoscopic cholecystectomy and perioperative endoscopic sphincterotomy.

Background: Laparoscopic cholecystectomy (LC) has become the reference treatment for biliary lithiasis, but the management strategy for common bile duct stones (CBDS) remains a subject of controversy in the absence of an established consensus. While conventional surgery remains the reference treatment for CBDS, minimally invasive techniques are becoming more and more popular. These methods consist of the extraction of the common bile duct stones either exclusively by laparoscopy or by sequential treatment with endoscopic sphincterotomy (ES) followed by LC.

[The remaining indications for open surgery in common bile duct lithiasis].

Once with the continuous development of mini-invasive procedures, the open surgery indications in the treatment of CBD stones are decreasing. Between January 1986 and December 1987, 514 patients with average age 60 years old (18-94) were treated for suspected or confirmed CBDS. Three distinctive periods were studied function of how the conventional surgery were either exclusive (group I), either together with the beginning era of laparoscopy (group II), or together with institutionalised laparoscopy (group III).

HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions.

Objective: To investigate HIV-1 infectivity in the natural environment of vaginal secretions.

Design: Vaginal wash samples collected from 14 healthy women were incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on CD4- ME180 cells derived from vaginal epithelium.

Methods: HIV-1 infectivity was measured by early virus growth in the various host cells tested using a quantitative p24 assay and by the Karber procedure.

Management of common bile duct stones by laparoscopic cholecystectomy and endoscopic sphincterotomy: pre-, per- or postoperative sphincterotomy?

Background/aims: The aim of this study was to evaluate the treatment of common bile duct stones (CBDS) by endoscopic sphincterotomy (ES) and laparoscopic cholecystectomy (LC), ES being performed either pre-, per- or postoperatively.

Methods: Between January 1990 and June 1997, 386 patients with a median age of 60 (range 18-92) years were treated for suspected or confirmed CBDS. The CBDS were uncomplicated in 264 cases (70%) but associated with a complication in 122 cases (30%), namely, cholangitis (69 cases) or acute pancreatitis (53 cases).

Detection and identification of human papilloma viral DNA, types 16, 18, and 33, by a combination of polymerase chain reaction and a colorimetric solid phase capture hybridisation assay.

A colorimetric microplate hybridization assay was developed previously to simplify detection procedures of DNA fragments resulting from polymerase chain reactions (PCR). This format has now been adapted for the simultaneous detection and identification of three human papillomavirus (HPV), types 16, 18 and 33, associated frequently with cervical cancer. This post-PCR detection system uses three type-specific capture oligonucleotides linked covalently to a single microplate well and three type-specific multibiotinylated oligonucleotidic probes for detection.

[Laparoscopic treatment of gastroesophageal reflux using fundoplication. Midterm results].

Unlabelled: The aim of this study was to see whether the results of surgical treatment of gastroesophageal reflux disease (GERD) by laparoscopic fundoplication were satisfactory and stable over time.

Patients And Methods: From July 1992 to September 1996, 161 patients with medical treatment-dependent GERD were operated. 17 patients were excluded from the study (conversion or immediate laparotomy).

[Results of fundoplication by laparoscopic approach in the treatment of gastroesophageal reflux. Apropos of 224 cases].

Study Aim: The aim of this paper is to evaluate prospectively immediate and 2-year results of laparoscopic fundoplicature (LF) for gastroesophageal reflux disease (GERD).

Patients And Methods: Patients presenting GERD who had been previously submitted to a long-term medical treatment were included in this study. Preoperative workup included upper GI tract endoscopy, esophageal manometry and 24-hour pHmetry.

[Outcome of surgical treatment of cancer of the stomach. Report of 330 cases].

The study concerned 330 cases of gastric adenocarcinoma operated from January 1969 to June 1996. Clinical, histological and therapeutic features were analyzed and compared during 3 periods (Group 1: 1969-79, Group 2: 1979-88, Group 3: 1989-96). The aim was to evaluate changes and results occurred in gastric carcinoma.