Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons.

Mutation of the ATL1 gene is one of the most common causes of hereditary spastic paraplegia (HSP), a group of genetic neurodegenerative conditions characterised by distal axonal degeneration of the corticospinal tract axons. Atlastin-1, the protein encoded by ATL1, is one of three mammalian atlastins, which are homologous dynamin-like GTPases that control endoplasmic reticulum (ER) morphology by fusing tubules to form the three-way junctions that characterise ER networks. However, it is not clear whether atlastin-1 is required for correct ER morphology in human neurons and if so what the functional consequences of lack of atlastin-1 are.

Potential drivers of the recent large Antarctic ozone holes.

The past three years (2020-2022) have witnessed the re-emergence of large, long-lived ozone holes over Antarctica. Understanding ozone variability remains of high importance due to the major role Antarctic stratospheric ozone plays in climate variability across the Southern Hemisphere. Climate change has already incited new sources of ozone depletion, and the atmospheric abundance of several chlorofluorocarbons has recently been on the rise.

AP-4 regulates neuronal lysosome composition, function, and transport via regulating export of critical lysosome receptor proteins at the trans-Golgi network.

The adaptor protein complex-4 or AP-4 is known to mediate autophagosome maturation through regulating sorting of transmembrane cargo such as ATG9A at the Golgi. There is a need to understand AP-4 function in neurons, as mutations in any of its four subunits cause a complex form of hereditary spastic paraplegia (HSP) with intellectual disability. While AP-4 has been implicated in regulating trafficking and distribution of cargo such as ATG9A and APP, little is known about its effect on neuronal lysosomal protein traffic, lysosome biogenesis, and function.

De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.

The endosomal sorting complexes required for transport (ESCRTs) are essential for multiple membrane modeling and membrane-independent cellular processes. Here we describe six unrelated individuals with de novo missense variants affecting the ATPase domain of VPS4A, a critical enzyme regulating ESCRT function. Probands had structural brain abnormalities, severe neurodevelopmental delay, cataracts, growth impairment, and anemia.

Laparoscopic bowel resection in the presence of a lumbo-peritoneal shunt: a rare case.

The presence of a cerebrospinal fluid (CSF) shunt was previously considered a contra-indication to laparoscopic surgery, however, case reports appeared that describe laparoscopic surgery proceeding with no adverse outcomes in such patients. The majority of these reports relate to laparoscopic cholecystectomy. Here we present what we believe to be only the second report of a patient undergoing laparoscopic bowel resection in the presence of a lumbo-peritoneal shunt.

HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation.

Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined mitophagy that is induced upon iron chelation and found that the transcriptional activity of HIF1α, in part through upregulation of BNIP3 and NIX, is an essential mediator of this pathway in SH-SY5Y cells.

ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic.

Mutations in the gene encoding the microtubule severing ATPase spastin are the most frequent cause of hereditary spastic paraplegia, a genetic condition characterised by length-dependent axonal degeneration. Here, we show that HeLa cells lacking spastin and embryonic fibroblasts from a spastin knock-in mouse model become highly polarised and develop cellular protrusions. In HeLa cells, this phenotype was rescued by wild-type spastin, but not by forms unable to sever microtubules or interact with endosomal ESCRT-III proteins.

Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e.

Long-term climate change in the D-region.

Controversy exists over the potential effects of long-term increases in greenhouse gas concentrations on the ionospheric D-region at 60-90 km altitudes. Techniques involving in-situ rocket measurements, remote optical observations, and radio wave reflection experiments have produced conflicting results. This study reports a novel technique that analyses long-distance subionospheric very low frequency radiowave observations of the NAA 24.

Mammalian mitophagy - from in vitro molecules to in vivo models.

The autophagic turnover of mitochondria, termed mitophagy, is thought to play an essential role in not only maintaining the health of the mitochondrial network but also that of the cell and organism as a whole. We have come a long way in identifying the molecular components required for mitophagy through extensive in vitro work and cell line characterisation, yet the physiological significance and context of these pathways remain largely unexplored. This is highlighted by the recent development of new mouse models that have revealed a striking level of variation in mitophagy, even under normal conditions.

Missing driver in the Sun-Earth connection from energetic electron precipitation impacts mesospheric ozone.

Energetic electron precipitation (EEP) from the Earth's outer radiation belt continuously affects the chemical composition of the polar mesosphere. EEP can contribute to catalytic ozone loss in the mesosphere through ionization and enhanced production of odd hydrogen. However, the long-term mesospheric ozone variability caused by EEP has not been quantified or confirmed to date.

Anal fistula plug: a prospective evaluation of success, continence and quality of life in the treatment of complex fistulae.

Aim: Curing complex anal fistula without compromising continence can be extremely challenging. This study investigated the healing rate, continence and quality of life of patients after treatment of complex anal fistula of cryptoglandular origin with a bioprosthetic plug.

Method: Consecutive patients were prospectively followed in four referral centres.

Abnormal colonic motility: a possible association with urge fecal incontinence.

Purpose: Fecal incontinence is a distressing condition affecting up to 7% of the population. Severe urgency is a symptom associated with hypersensitivity of the rectum, a common finding in both fecal incontinence and irritable bowel syndrome. The purpose of this study was to investigate whether patients with fecal incontinence, urgency, and rectal hypersensitivity have abnormal hindgut motility, suggestive of a more generalized motility problem.

Who supports tobacco excise taxes? Factors associated with towns' and individuals' support in Massachusetts.

Objectives: The authors examined factors related to public support for cigarette taxes: smoking behavior, attitudes about other tobacco control policies, and sociodemographic factors.

Methods: The authors regressed referendum voting outcomes on sociodemographic characteristics of Massachusetts' 351 towns. Logistic regressions on the surveys of Massachusetts adults (N = 14,000+) showed support for hypothetical tax increases to be related to respondents' smoking status, support for other tobacco control policies, and sociodemographic characteristics.

Accuracy of thin section magnetic resonance using phased-array pelvic coil in predicting the T-staging of rectal cancer.

Magnetic resonance (MR) imaging may contribute to staging rectal cancer and inform the decision regarding administration of pre-operative radiotherapy. The accuracy of MR has been debated. The aim of the present study was to determine the accuracy of thin section T2-weighted MR images in rectal cancer patients.

Electrocardiographic abnormalities and uremic cardiomyopathy.

Background: Progressive renal disease is associated with an increased risk of cardiovascular death, specifically sudden death. We investigated the link between uremic cardiomyopathy, QT interval and dispersal, and arrhythmias (by ambulatory ECG monitoring) in patients at different stages of progressive renal disease.

Methods: In a cross-sectional study we investigated 296 patients with nondiabetic renal disease (53 transplant recipients, 55 hemodialysis patients, and 188 throughout the range of chronic renal failure).

Deterioration in renal function following commencement of citalopram.

We report the case of an 85 year old woman, admitted to hospital with a two month history of a depressive illness. Within one week of commencing treatment with citalopram 20mg daily, she had developed a widespread rash, bilateral ankle oedema and a range of biochemical and haematological abnormalities, including marked elevations of plasma urea and creatinine and increased neutrophil and eosinophil counts. Following withdrawal of citalopram, her physical state returned to normal within two weeks.

Silver(I) carboxylates: versatile inorganic analogs of carboxylic acids for supramolecular network formation.

Dimeric motifs formed by silver(I) carboxylates, illustrated here by the unit Ag2(CF3CO2)2, resemble the well known dimerization of carboxylic acids, i.e. 'H2(RCO2)2', but exhibit greater flexibility, while permitting further elaboration into neutral coordination networks through linkage of the silver centres via ditopic ligands.

Isolation and structure elucidation of two new calpain inhibitors from Streptomyces griseus.

Two new peptides, a diketopiperazine of N-methyltyrosine (1) and a tetrapeptide containing N-methyltyrosine (2), were isolated from an actinomycete strain Streptomyces griseus. These compounds inhibit the enzyme calpain in the micromolar range and were characterized on the basis of spectroscopic analysis, amino acid analysis and sequencing. The structure of the tetrapeptide N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine (2), was also confirmed by total synthesis.

Is there a delay in the onset of the antidepressant effect of electroconvulsive therapy?

The severity of depression in 11 drug-free unipolar patients diagnosed with definite major depressive disorder was assessed using the Hamilton Rating Scale for Depression during a course (5-10 treatments) of bilateral electroconvulsive therapy (ECT). The degree of improvement after three treatments of ECT was six times greater than the improvement that occurred over the remainder of the course. Although depressed patients who recover with ECT require repeated treatments, the treatments early in a course of ECT can have marked antidepressant effect.

Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice.

The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti-epileptic drugs were also examined.