Miracle-dz/UniFAR-FTUs huggingface dataset:
Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A)

We have recently reported a missense mutation in exon 4 of the tubulin alpha 1A (Tuba1a) gene in a hyperactive N‐ethyl‐N‐nitrosourea (ENU) induced mouse mutant with abnormal lamination of the hippocampus. Neuroanatomical similarities between the Tuba1a mutant mouse and mice deficient for Doublecortin (Dcx) and Lis1 genes, and the well‐established functional interaction between DCX and microtubules (MTs), led us to hypothesize that mutations in TUBA1A (TUBA3, previous symbol), the human homolog of Tuba1a, might give rise to cortical malformations. This hypothesis was subsequently confirmed by the identification of TUBA1A mutations in two patients with lissencephaly and pachygyria, respectively. Here we report additional TUBA1A mutations identified in six unrelated patients with a large spectrum of brain dysgeneses. The de novo occurrence was shown for all mutations, including one recurrent mutation (c.790C>T, p.R264C) detected in two patients, and two mutations that affect the same amino acid (c.1205G>A, p.R402H; c.1204C>T, p.R402C) detected in two other patients. Retrospective examination of MR images suggests that patients with TUBA1A mutations share not only cortical dysgenesis, but also cerebellar, hippocampal, corpus callosum, and brainstem abnormalities. Interestingly, the specific high level of Tuba1a expression throughout the period of central nervous system (CNS) development, shown by in situ hybridization using mouse embryos, is in accordance with the brain‐restricted developmental phenotype caused by TUBA1A mutations. All together, these results, in combination with previously reported data, strengthen the relevance of the known interaction between MTs and DCX, and highlight the importance of the MTs/DCX complex in the neuronal migration process. Hum Mutat 28(11), 1055–1064, 2007. © 2007 Wiley‐Liss, Inc.
Aspartate and maltose-binding protein interact with adjacent sites in the Tar chemotactic signal transducer of Escherichia coli

The Tar protein of Escherichia coli is a chemotactic signal transducer that spans the cytoplasmic membrane and mediates responses to the attractants aspartate and maltose. Aspartate binds directly to Tar, whereas maltose binds to the periplasmic maltose-binding protein, which then interacts with Tar. The Arg-64, Arg-69, and Arg-73 residues of Tar have previously been shown to be involved in aspartate sensing. When lysine residues are introduced at these positions by site-directed mutagenesis, aspartate taxis is disrupted most by substitution at position 64, and maltose taxis is disrupted most by substitution at position 73. To explore the spatial distribution of ligand recognition sites on Tar further, we performed doped-primer mutagenesis in selected regions of the tar gene. A number of mutations that interfere specifically with aspartate taxis (Asp-), maltose taxis (Mal-), or both were identified. Mutations affecting residues 64 to 73 or 149 to 154 in the periplasmic domain of Tar are associated with an Asp- phenotype, whereas mutations affecting residues 73 to 83 or 141 to 150 are associated with a Mal- phenotype. We conclude that aspartate and maltose-binding protein interact with adjacent and partially overlapping regions in the periplasmic domain of Tar to initiate attractant signalling.
Clearance of Inhaled Potassium Octatitanate Whisker from Rat Lungs

Clearance of Inhaled Potassium Octatitanate Whisker from Rat Lungs: Hiroshi Yamato, et al. Department of Environmental Health Engineering, University of Occupational and Environmental Health, Japan—The clearance rate of inhaled man‐made fibers (MMFs) is one of the important factors for predicting health hazards in human. Potassium octatitanate whisker is a newly developed MMF in Japan with strong resistance to heat and chemicals. Two types of commercially sold potassium octatitanate whisker were used in this study. In order to examine the rate of clearance of this whisker, rats were exposed to whisker aerosol for 4 weeks and the rate of clearance of inhaled whiskers from rat lungs was examined in terms of the fiber mass clearance rate and dimensional change in whiskers. The decrease in fiber mass retained in rat lungs was expressed with a two‐compartment model. As for the dimensional change in whiskers, no decrease was observed in diameter and no surface change due to dissolution was detected over the 12‐month observation period. Macrophage mediated clearance was thought to be the main mechanism for the clearance of potassium octatitanate whiskers.
Thrombotic thrombocytopenic purpura - analysis of clinical features, laboratory characteristics and therapeutic outcome of 24 patients treated at a Tertiary Care Center in Saudi Arabia

Objective: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients Methods: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC). Results: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR. Conclusion: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities.
Growth pattern and risk of schizophrenia

Background Foetal nutrition and growth seem to affect the risk of developing schizophrenia. Exposure to famine during foetal development and low birthweight increase the risk. However, few studies have investigated the association between schizophrenia and adult height and weight or patterns of growth. Method The study population consisted of two subpopulations: families with at least one member with schizophrenia, and families of offspring of mothers with psychotic disorder, and controls. Using a seven-parameter model of height growth curves, we compared the parameters of persons who later developed schizophrenia and their unaffected siblings from the same families. We also studied how growth curve parameters differed in children with genetic risk for schizophrenia and controls, and whether weight, height and body mass index (BMI) at different ages predicted later development of schizophrenia. Results The predicted growth curves based on a parametric model were nearly identical for persons with schizophrenia and their unaffected siblings. Adult height of daughters of mothers with psychoses was borderline significantly (p=0.0536) lower compared to controls, while no difference was detected among sons (p=0.3283). Conclusions No association between growth characteristics and schizophrenia in families with at least one member with schizophrenia was found. Family-related factors should be taken into account as possible confounders in future studies on growth and schizophrenia.
Neuropathology and Neurodegeneration in Rodent Brain Induced by Lentiviral Vectormediated Overexpression of α‐Synuclein

Two mutations in α‐synuclein, the main constituent of Lewy bodies, have been identified in familial Parkinson's disease. We have stereotactically injected lentiviral vectors encoding wild‐type and A30P mutant human α‐synuclein in different brain regions (striatum, substantia nigra, amygdala) of mice. Overexpression of α‐synuclein induced timedependent neuropathological changes reminiscent of Lewy pathology: abnormal accumulation of α‐synuclein in cell bodies and neurites, α‐synuclein‐positive neuritic varicosities and cytoplasmic inclusions that stained with ubiquitin antibodies and became larger and more frequent with time. After one year, α‐synuclein‐ and ubiquitin‐positive neurons displayed a degenerative morphology and a significant loss of α‐synuclein‐positive cells was observed. Similar findings were observed with both the wild‐type and the A30P mutant form of α‐synuclein and this in different brain regions. This indicates that overexpression of α‐synuclein is sufficient to induce Lewy‐like pathology and neurodegeneration and that this effect is not restricted to dopaminergic cells. Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases.
Representation and Integration of New Political Issues in Party Systems : Analyses of New Challenger Parties in 15 West European Democracies (代表と統合の政治変容)

: Advanced democracies have witnessed new types of political issues being represented and integrated in their party systems in the past decades. Yet, their patterns still remain unknown as to the conditions in which new political issues are first represented and eventually integrated in each party system. To fill this gap, this article illustrates such patterns through different phases of socio-economic transformation, party system responses to newly emerging issues, and electoral systems’ openness. By applying a ‘double-hurdle’ model, the article tries to elucidate the mechanisms in which new political issues are represented in the first hurdle and then integrated in party systems in the second hurdle. The analyses of new challenger parties across 15 West European democracies revealed that New Politics issues are represented through New Politics Parties (NPPs) when existing party systems are not responsive to the new issues but NPPs further grow and New Politics issues are integrated in party systems when existing party systems are more responsive to these newly emerging issues. Likewise, different conditions mattered differently for the representation and growth hurdles for both NPPs and Extreme Right Parties (ERPs).
Risk factors for acute graft‐versus‐host disease

Summary. Acute graft‐versus‐host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA‐identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2‐year actuarial probability was 54% (95% confidence interval 52–56%) for absent or mild and 46% (44–48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex‐match (female→male greater than others, relative risk 2.0, P<0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P<0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P<0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female→male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P<0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.
Are twitches, startles, and body movements pain indicators in extremely low birth weight infants?

OBJECTIVE The goal of this study was to examine whether body activity such as postural, trunk, and limb movements may be potential pain cues in preterm infants. DESIGN Convenience sample. SETTING Level III neonatal intensive care unit (NICU). PATIENTS Extremely low birth weight (< or = 1,000 g) preterm infants (n = 64) undergoing routine NICU medical care. OUTCOME MEASURES Procedures likely to differ in evoking distress (i.e., endotracheal suctioning, chest physical therapy, diaper change, or nasogastric feed) were observed. Behaviors were recorded at bedside using the Neonatal Individualized Developmental Care and Assessment Program system. RESULTS Changes in heart rate and sleep/waking state were related to the procedures, supporting the assumption of differing relative disruption to the infant. Arching, squirming, startles, and twitching were not observed significantly more during procedures than at baseline. After controlling for background variables, finger splay and leg extension were significantly related to ongoing procedures. Facial brow raising was a function of the number of invasive procedures in the past 24 hours; thus, it may be a useful cue of sensitization. CONCLUSIONS Some extensor movements seemed to be distress signals, whereas tremors, startles, and twitches were not related to discomfort during the observation period. These behaviors may differ qualitatively during longer lasting tissue invasive events. The results of this study indicate the need for more in-depth study of patterns of motor activity in preterm infants over longer observation periods to evaluate potential signs of stress and pain in babies undergoing NICU medical care.
Changes in the rumen metabolism of sheep given increasing amounts of linseed oil in their diet

1. Linseed oil was incorporated gradually into the diet of four sheep until the animals received 90 g additional fat/d. Attempts were made to measure changes in concentration of substances and rates of synthesis in the rumen directly, and by incubation of rumen contents in vitro (zero-time technique). 2. The high-fat diet increased the dilution rate and the volume of rumen contents and decreased the synthesis of diaminopimelic acid in the rumen. The number of protozoa decreased and the number of bacteria increased in the rumen of animals receiving the high-fat diet. 3. The concentration of volatile fatty acids (VFA) in the rumen decreased for sheep given the high-fat diet, but the capacity of rumen contents to produce VFA in vitro increased. 4. The incorporation of radioactivity from [14C]acetate into lipids during incubation of rumen contents in vitro increased with the amount of linseed oil in the diet. The greatest proportional increase was with the bacterial fraction of rumen contents. 5. In the group of four animals used, one animal showed consistent differences in the magnitude of the measured variables. This animal appeared to have a smaller rumen, a lower dilution rate and larger concentrations of some substances in the rumen. A higher proportion of fatty acids appeared to be synthesized by the micro-organisms from this animal.
The male versus female perspective on family planning: Kinshasa, Zaire

Summary Males have often been neglected in both family planning programmes and in surveys used to design and evaluate such programmes. A 1988 study on fertility, family planning and AIDS in Kinshasa, Zaire, provides comparable data on 3140 men and 3485 women of reproductive age which served as the basis for analysing male/female differences. The study indicated a fair degree of similarity in the attitudes, beliefs, knowledge levels and practices of men and women regarding fertility and family planning. Where they differed (e.g. on expected or ideal number of children, the desire for more children at parity 7 or above), men tended to be more pronatalist than women. The implications of the findings for future family planning programmes are discussed. Programmes should target males because of their role as decision makers within Zairian society.
Bone mineral density of the mandible in ovariectomized rats: analyses using dual energy X-ray absorptiometry and peripheral quantitative computed tomography.

INTRODUCTION Although previous studies have shown that maxillary molar extraction in ovariectomized (OVX) animals causes mandibular loss of bone, it is still questionable as to whether estrogen deficiency affects mandibles with functional occlusion. MATERIALS AND METHODS To answer this question, 13-week-old female Sprague-Dawley rats were bilaterally OVX or sham-operated. After 109 days, the bone mineral density (BMD) of the femurs and mandibles was measured using dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). RESULTS In DEXA analysis, although the BMD of the total mandible of the OVX rats was similar to that of the sham-operated rats, the BMD of the condylar region in the OVX rats had decreased by 12.5%. In pQCT analysis, decrease in trabecular BMD of the mandibular bone was detectable but low in the molar region (maximal 13%), whereas no difference was seen in cortical BMD. In the femurs, the trabecular bone prominently decreased in OVX rats (30% decrease in pQCT analysis) as previously reported. CONCLUSION This study revealed regional differences in the mandibular bone decrease in OVX rats. Although the mechanism of low susceptibility of the mandible to estrogen-deficient conditions remains unknown, it is likely that mechanical stress derived from functional occlusion is preventing bone loss in this pathological condition. Furthermore, this study demonstrated the advantage of pQCT in analyzing rat mandibular bone.
Reproduction of Globodera rostochiensis (Woll.) Behrens on resistant and susceptible potatoes in Finland

Susceptible and resistant (H1) potato cultivars were grown in nematode-infested experimental fields in Northern and Southern Finland. The resistant cultivars yielded well in Southern Finland, and they also satisfactorily reduced the nematode populations. In the northern experimental field at the Arctic Circle the nematode population decreased and seemed to disappear, as it also did under susceptible potatoes. Soil temperature and the length of the growing season are not sufficient for the potato cyst nematodes to establish and reproduce in the northern parts of Finland. Further studies on the population biology of potato cyst nematodes in northern regions are needed due to the importance of these areas in the production of seed potatoes.
Continuous lenalidomide treatment for newly diagnosed multiple myeloma.

BACKGROUND Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma. METHODS We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival. RESULTS The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP. CONCLUSIONS MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.).
Hepatitis E Virus: Foodborne, Waterborne and Zoonotic Transmission

Hepatitis E virus (HEV) is responsible for epidemics and endemics of acute hepatitis in humans, mainly through waterborne, foodborne, and zoonotic transmission routes. HEV is a single-stranded, positive-sense RNA virus classified in the family Hepeviridae and encompasses four known Genotypes (1–4), at least two new putative genotypes of mammalian HEV, and one floating genus of avian HEV. Genotypes 1 and 2 HEVs only affect humans, while Genotypes 3 and 4 are zoonotic and responsible for sporadic and autochthonous infections in both humans and several other animal species worldwide. HEV has an ever-expanding host range and has been identified in numerous animal species. Swine serve as a reservoir species for HEV transmission to humans; however, it is likely that other animal species may also act as reservoirs. HEV poses an important public health concern with cases of the disease definitively linked to handling of infected pigs, consumption of raw and undercooked animal meats, and animal manure contamination of drinking or irrigation water. Infectious HEV has been identified in numerous sources of concern including animal feces, sewage water, inadequately-treated water, contaminated shellfish and produce, as well as animal meats. Many aspects of HEV pathogenesis, replication, and immunological responses remain unknown, as HEV is an extremely understudied but important human pathogen. This article reviews the current understanding of HEV transmission routes with emphasis on food and environmental sources and the prevalence of HEV in animal species with zoonotic potential in humans.
Learning for sustainability through CIDA's “Community-based pest management in Central American agriculture” project: a deliberative, experiential and iterative process

Community-based approaches to environmental management provide opportunities for public engagement in local decision-making processes. This qualitative case study examines learning as resulted from participation in CIDA's “Community-based pest management in Central American agriculture” project. Outcomes include learning about alternative farming practices, human and natural environments, and safer pesticide use. Many participants learnt how to work more effectively with rural communities. For some, this changed their perspective about life and their role in society. Activities that fostered learning outcomes, including sustainability-related outcomes, were: planning and implementing project activities, experimenting on farm demonstration plots, participating in outreach workshops, and students doing rural practica. The learning process, involving international university collaborators and rural participants, is analyzed particularly as it relates to cultural context, collective action, and sustainability. Findings affirm that how the public participates in environmental management decisions influences the breadth and depth of learning outcomes; practical and policy implications are discussed.