bluuebunny/crossref_metadata_2025 huggingface dataset:
Two novel unstable hemoglobin variants due to in‐frame deletions of key amino acids in the β‐globin chain
Authors: Scheps Karen G. , Hasenahuer Marcia Anahí , Parisi Gustavo , Targovnik Héctor M. , García Eliana , Veber Ernesto Samuel , Crisp Renée , Elena Graciela , Varela Viviana , Fornasari María Silvina
Published: January 2018

Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in‐frame deletions, leading to β‐globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC‐Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α‐helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia.
On the history and future of soil organic phosphorus research: a critique across three generations
Authors: Haygarth P. M. , Harrison A. F. , Turner B. L.
Published: January 2018

Soil organic phosphorus has broad agronomic and ecological significance, but remains a neglected topic of research. This opinion paper reflects a collaborative discussion between three generations of scientists who have collectively studied soil organic phosphorus for almost 50 years. We discuss personal reflections on our involvement in the field, opinions about progress and promising opportunities for future research. We debate an apparent overemphasis on analytical methodology at the expense of broader questions, and whether this has stifled progress in recent decades. We reiterate the urgent need to understand organic phosphorus cycling in the environment to address fundamental questions about phosphate supply, crop nutrition, water quality and ecosystem ecology. We also contend that we must encourage and integrate the study of organic phosphorus across all scales, from molecular chemistry to global cycling. Our discussion among three generations of researchers shows the value of a long‐term perspective, emphasizes the changing nature of this field of research, and reinforces the importance of continuing to be curious about the dynamics of organic phosphorus in the environment.

Highlights

Critical evaluation of the current state of soil organic phosphorus research

Collective views of three researchers whose careers span 50 years

Research is driven by analytical development, but will benefit from broader conceptual approaches

We emphasize the value of long‐term and broad‐scale perspectives on this important research topic
Defining the phenotypic spectrum of SLC6A1 mutations
Authors: Johannesen Katrine M. , Gardella Elena , Linnankivi Tarja , Courage Carolina , de Saint Martin Anne , Lehesjoki Anna‐Elina , Mignot Cyril , Afenjar Alexandra , Lesca Gaetan , Abi‐Warde Marie‐Thérèse , Chelly Jamel , Piton Amélie , Merritt J. Lawrence , Rodan Lance H. , Tan Wen‐Hann , Bird Lynne M. , Nespeca Mark , Gleeson Joseph G. , Yoo Yongjin , Choi Murim , Chae Jong‐Hee , Czapansky‐Beilman Desiree , Reichert Sara Chadwick , Pendziwiat Manuela , Verhoeven Judith S. , Schelhaas Helenius J. , Devinsky Orrin , Christensen Jakob , Specchio Nicola , Trivisano Marina , Weber Yvonne G. , Nava Caroline , Keren Boris , Doummar Diane , Schaefer Elise , Hopkins Sarah , Dubbs Holly , Shaw Jessica E. , Pisani Laura , Myers Candace T. , Tang Sha , Tang Shan , Pal Deb K. , Millichap John J. , Carvill Gemma L. , Helbig Kathrine L. , Mecarelli Oriano , Striano Pasquale , Helbig Ingo , Rubboli Guido , Mefford Heather C. , Møller Rikke S.
Published: January 2018

Objective

Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1‐mutated patients.

Methods

We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.

Results

Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure‐free, with valproic acid being the most effective drug. There was no clear‐cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5‐3.5 Hz spikes/polyspikes‐and‐slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).

Significance

Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
Cytotoxic edema at onset in West syndrome of unknown etiology: A longitudinal diffusion tensor imaging study
Authors: Ogawa Chikako , Kidokoro Hiroyuki , Fukasawa Tatsuya , Yamamoto Hiroyuki , Ishihara Naoko , Ito Yuji , Sakaguchi Yoko , Okai Yu , Ohno Atsuko , Nakata Tomohiko , Azuma Yoshiteru , Hattori Ayako , Kubota Tetsuo , Tsuji Takeshi , Hirakawa Akihiro , Kawai Hisashi , Natsume Jun
Published: January 2018

Objective

To clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology.

Methods

Diffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract‐based spatial statistics (TBSS) and tract‐specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age‐matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q‐value).

Results

TBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both).

Significance

These findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS.
Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons
Authors: Al‐Muhtasib Nour , Sepulveda‐Rodriguez Alberto , Vicini Stefano , Forcelli Patrick A.
Published: January 2018

Objective

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. The use of phenobarbital continues despite growing evidence that it exerts suboptimal seizure control and is associated with long‐term alterations in brain structure, function, and behavior. Alterations following neonatal phenobarbital exposure include acute induction of neuronal apoptosis, disruption of synaptic development in the striatum, and a host of behavioral deficits. These behavioral deficits include those in learning and memory mediated by the hippocampus. However, the synaptic changes caused by acute exposure to phenobarbital that lead to lasting effects on brain function and behavior remain understudied.

Methods

Postnatal day (P)7 rat pups were treated with phenobarbital (75 mg/kg) or saline. On P13‐14 or P29‐37, acute slices were prepared and whole‐cell patch‐clamp recordings were made from CA1 pyramidal neurons.

Results

At P14 we found an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in the phenobarbital‐exposed as compared to the saline‐exposed group. In addition to this change in mIPSC frequency, the phenobarbital group displayed larger bicuculline‐sensitive tonic currents, decreased capacitance and membrane time constant, and a surprising persistence of giant depolarizing potentials. At P29+, the frequency of mIPSCs in the saline‐exposed group had increased significantly from the frequency at P14, typical of normal synaptic development; at this age the phenobarbital‐exposed group displayed a lower mIPSC frequency than did the control group. Spontaneous inhibitory postsynaptic current (sIPSC) frequency was unaffected at either P14 or P29+.

Significance

These neurophysiological alterations following phenobarbital exposure provide a potential mechanism by which acute phenobarbital exposure can have a long‐lasting impact on brain development and behavior.
Climate change and interspecific interactions drive species alternations between anchovy and sardine in the western North Pacific: Detection of causality by convergent cross mapping
Authors: Nakayama Shin‐Ichiro , Takasuka Akinori , Ichinokawa Momoko , Okamura Hiroshi
Published: January 2018

The abundance and recruitment of anchovy Engraulis spp. and sardine Sardinops spp. alternate in a synchronized way across the Pacific. Convergent cross mapping (CCM) indicated that climate change drives the alternation of the two species in the California Current System. However, climate indices patterns in the western North Pacific contrast with those in the eastern North Pacific, despite synchronous species alternations occurring. Therefore, it is of great interest to clarify whether climate change, or any other factors, affects the population dynamics of Japanese anchovy and Japanese sardine in the western North Pacific. Using CCM, we tested whether climate change and interspecific interactions affect the population dynamics of these two species. We found that climate change affected recruitment, and we clarified the spatiotemporal pattern of this effect. This result supports the existing hypotheses that population dynamics are regulated by climate change in the western North Pacific. The present study also detected interspecific interactions between sardine and anchovy, which might promote the alternation of the two species, and has not been reported in other regions.
Regional forcing explains local species diversity and turnover on tropical islands
Authors: Ibanez Thomas , Keppel Gunnar , Baider Cláudia , Birkinshaw Chris , Culmsee Heike , Cordell Susan , Florens F. B. Vincent , Franklin Janet , Giardina Christian P. , Gillespie Thomas W. , Laidlaw Melinda , Litton Creighton M. , Martin Tara G. , Ostertag Rebecca , Parthasarathy Narayanaswamy , Randrianaivo Richard , Randrianjanahary Miramasoandro , Rajkumar Muthu , Rasingam Ladan , Ratovoson Fidy , Reza Ludovic , Sack Lawren , Aiba Shin‐ichiro , Webb Edward , Whitfeld Timothy J. S. , Zang Runguo , Birnbaum Philippe
Published: January 2018

Aim

To determine the role of regional forcing on plot‐level species diversity and composition, and to quantify the relative importance of biogeographical and climatic factors in explaining woody plant diversity and composition at the local‐, island‐ and archipelago‐scale.

Location

Forty‐one tropical islands of the Indo‐Pacific region from Madagascar to Hawai‘i Island.

Methods

We analysed the diversity and composition of tropical woody plant communities located across 113 plots, 41 islands and 19 archipelagos. We used generalized linear mixed‐effects models and generalized dissimilarity models to determine the role of regional forcing at the island and archipelago scale and to assess the relative importance of biogeographical (area and isolation of islands or archipelagos, geographical distance between plots) and climatic factors in explaining differences in local diversity and composition (species turnover). Analyses were conducted at different geographical scales (local, island and archipelago) and taxonomic levels (species, genus and family).

Results

Variation in local (plot‐level) diversity (as species density, the number of species per 100 woody plants) was primarily explained by island and archipelago identity. Maximum species density was positively correlated with the area of an island (or archipelago) and negatively correlated with the isolation of an archipelago. Local climatic variability was also a significant predictor of species density, but less important than regional forcing. Climate variables explained < 20% of the variation in species turnover across all plots. The importance of geographical distance between plots relative to climate in driving species turnover decreased from the species to family level, and from the regional to island level.

Main conclusions

Regional forcing was the key driver of local diversity and composition on islands. Island area and archipelago isolation are likely driving local diversity through their effects on the pool of island species. Geographical distance between plots is the main factor explaining species turnover, while at higher taxonomic levels, climatic factors and niche conservatism are the main drivers.
Deletion of endoplasmic reticulum stress‐responsive co‐chaperone p58IPK protects mice from diet‐induced steatohepatitis
Authors: Bandla Harikrishna , Dasgupta Debanjali , Mauer Amy S. , Nozickova Barbora , Kumar Swarup , Hirsova Petra , Graham Rondell P. , Malhi Harmeet
Published: January 2018

Aim

Activation of PKR‐like endoplasmic reticulum kinase (PERK), an endoplasmic reticulum stress sensor, is a feature of non‐alcoholic steatohepatitis (NASH), yet regulators of PERK signaling remain undefined in this context. The protein p58IPK regulates PERK; however, its role in NASH has not been examined. The aim of this study was to assess the in vivo role of p58IPK in the pathogenesis of dietary NASH.

Methods

Parameters of hepatocyte cell death, liver injury, inflammation, fibrosis, indirect calorimetry and PERK activation were assessed in p58IPK knockout (p58ipk−/−) mice and their wild‐type littermate controls. All animals were fed a diet enriched in fat, fructose, and cholesterol (FFC) for 20 weeks.

Results

Activation of PERK was attenuated in FFC‐fed p58ipk−/− mice. Accordingly, FFC‐fed p58ipk−/− mice showed a reduction in hepatocyte apoptosis and death receptor expression, with a significant reduction in serum alanine transaminase values. Correspondingly, macrophage accumulation and fibrosis were significantly lower in FFC‐fed p58ipk−/− mice.

Conclusion

We have shown that, in an in vivo dietary NASH model, p58IPK mediates hepatocyte apoptosis and liver injury, likely through PERK phosphorylation. In the absence of p58IPK, PERK phosphorylation and NASH are attenuated. Inhibition of hepatic p58IPK could be a future target for NASH therapy.
Dermoscopic characterization of cutaneous lymphomas: a pilot survey
Authors: Ghahramani Grant K. , Goetz Kirsten E. , Liu Vincent
Published: January 2018

Background

While substantial dermoscopic analysis of melanocytic lesions has been performed, dermoscopic characterization of cutaneous lymphoid proliferations has been limited. Cutaneous lymphoma, particularly early mycosis fungoides (MF) and its variants, is often challenging to clinically and pathologically distinguish from inflammatory processes of the skin. This study aimed to survey the dermoscopic findings of cutaneous lymphomas and to discern whether any patterns might potentially serve as specific signatures.

Methods

Fifteen patients with an established diagnosis of cutaneous lymphoma were prospectively recruited and seen in the university multidisciplinary cutaneous lymphoma program with MF, an MF‐ variant, CD30‐positive lymphoproliferative disorder, or cutaneous B‐cell lymphomas and were included in our study. Dermoscopic findings, histologic features, clinical characteristics, and demographic data were analyzed.

Results

Patch stage MF was characterized by interconnected white structureless patches encircling small fine linear vessels, yielding an overall trabeculated to fenestrated pattern under dermoscopy. Corresponding histopathologic findings for these patterns included epidermotropism, atypical pleomorphic cells, and lichenoid infiltrates. Folliculotropic mycosis fungoides (FMF) was characterized by folliculocentric erosions surrounded by dotted and fine linear vessels, loss of terminal follicles, comedo‐like openings, and interconnected regular‐appearing structureless patches. Corresponding histopathologic findings in these FMF cases were typical of FMF. Notably, these changes were not appreciated in lymphomatoid papulosis. Primary cutaneous follicle center B cell lymphoma showed crystalline structures and vascular pseudopods.

Conclusions

Cutaneous lymphomas appear to demonstrate characteristic dermoscopic patterns, reflective of the specific lymphoma type and its corresponding histopathology, which have not been seen in inflammatory skin conditions, such as psoriasis and eczematous dermatitis.
Efficacy and safety of noncultured melanocyte‐keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence
Authors: Vakharia Paras P. , Lee Dylan E. , Khachemoune Amor
Published: January 2018

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte‐keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001–2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in‐depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.
Differences in pre‐service teachers' knowledge and readiness to use ICT in education
Authors: Valtonen Teemu , Kukkonen Jari , Kontkanen Sini , Mäkitalo‐Siegl Kati , Sointu Erkko
Published: January 2018

The aim of this paper is to provide insights into differences between pre‐service teachers based on the areas of technological pedagogical content knowledge (TPACK) and the areas of theory of planned behaviour (TPB) in the context of using information and communication technology in education. The target group consisted of 267 first‐year pre‐service teachers at 3 Finnish universities. Differences between pre‐service teachers were outlined using cluster analysis based on their knowledge of different TPACK areas (the respondents' weak and strong areas). To see how the TPB areas aligned with the 4 TPACK clusters, 1‐way analysis of variance was used. Statistically significant differences between the 4 clusters were found in all the TPB areas except subjective norms. These results provide insights into the differences among pre‐service teachers in the context of TPACK and the TPB. They also suggest that instead of considering pre‐service teachers as one homogenous group, we need to understand the variations among their abilities and knowledge in order to be able to provide them with support they need within teacher education.
Larvicidal activities of limonoids from Turraea abyssinica (Meliaceae) on Tuta absoluta (Meyrick)
Authors: Essoung F. R. E. , Chhabra S. C. , Mba'ning B. M. , Mohamed S. A. , Lwande W. , Lenta B. N. , Ngouela S. A. , Tsamo E. , Hassanali A.
Published: January 2018

Preliminary screening of extracts of the leaves and stems of four Turraea plant species (Meliaceae) on second instar larvae of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) showed that the methanolic extract of Turraea abyssinica leaves possess good toxic potential with LD50 of 270.7 ppm. Fractionation of this extract led to isolation of a new limonoid derivative, 12α‐diacetoxywalsuranolide (1) and three other known limonoids [1α,7α,12α‐triacetoxy‐4α‐carbomethoxy‐11β‐hydroxy‐14β,15β‐epoxyhavanensin (2), 11‐epi‐21‐hydroxytoonacilide (3), 11β,12α‐diacetoxycedrelone (4)]. The structures of the compounds were established by IR, UV, mass spectrometry and 1D/2D NMR analyses, and in the case of the known compounds, also by comparison with reported data. All the isolates were tested for their larvicidal activities at different dose range against second instar larvae of T. absoluta. They were found to be more active (with LD50 < 7.0 ppm) compared to the reference compound azadirachtin (LD50 value of 7.8 ppm).
Complexity in internal medicine wards: A novel screening method and implications for management
Authors: Bandini Fabrizio , Guidi Stefano , Blaszczyk Silvia , Fumarulo Antonietta , Pierini Michela , Pratesi Paolo , Spolveri Stefano , Padeletti Margherita , Petrone Pasquale , Zoppi Paolo , Landini Giancarlo
Published: January 2018

Rationale

Complexity is increasingly recognized as a critical variable in health care. However, there is still lack of practical tools to assess it and tackle the challenges that stem from it, particularly within hospitals.

Aims and objective

To validate a simple novel screening method based on both objective and subjective criteria to identify patients with clinically complex hospitalization events. To evaluate the prevalence of patients with complex events, identify their features, and compare them with those of the other patients and to those of patients with multimorbidities.

Method

We monitored the level of complexity of the hospitalization events of 240 patients admitted to an internal medicine ward in Tuscany over the course of 56 days. We compared the demographic features, the length of stay, and the prognosis of patients with and without complex events.

Results

Sixty‐nine patients (28.8% of the sample) had a complex episode during their stay, and 115 (47.9%) had phases of low complexity. Patients with complex episodes were younger and more comorbid than patients without. They stayed longer in‐hospital (+4.5 days; 95% CI: 2.5‐6.5) and had higher mortality (OR: 24.93; 95% CI: 6.97‐171.63) and a lower probability of home discharge (OR: 0.25; 95% CI: 0.13‐0.48).

Conclusions

The results show that using a simple screening method is possible to identify complex patients within IM wards and that every day, about one‐third of the patients are complex. The results are discussed in implications for the dynamic management of patients with complex and simple phases during hospitalization.
First identification and characterization of Streptococcus iniae obtained from tilapia (Oreochromis aureus) farmed in Mexico
Authors: Ortega C , García I , Irgang R , Fajardo R , Tapia‐Cammas D , Acosta J , Avendaño‐Herrera R
Published: January 2018

This is the first study to isolate, identify and characterize Streptococcus iniae as the causative disease agent in two tilapia (Oreochromis aureus) populations. The populations were geographically isolated, of distinct origins, and did not share water sources. Affected fish showed various external (e.g., exophthalmia and cachexia, among others) and internal (e.g., granulomatous septicaemia and interstitial nephritis, among others) signs. All internal organ samples produced pure cultures, two of which (one from each farm, termed S‐1 and S‐2) were subjected to biochemical, PCR and 16S rRNA sequencing (99.5% similarity) analyses, confirming S. iniae identification. The two isolates presented genetic homogeneity regardless of technique (i.e., RAPD, REP‐PCR and ERIC‐PCR analyses). Pathogenic potentials were assessed through intraperitoneal injection challenges in rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio). Rainbow trout mortalities were respectively 40% and 70% at 104 and 106 CFU per fish with the S‐1 isolate, while 100% mortality rates were recorded in zebrafish at 102 and 104 CFU per fish with the S‐2 isolate. The obtained data clearly indicate a relationship between intensified aquaculture activities in Mexico and new disease appearances. Future studies should establish clinical significances for the tilapia industry.
Rise and fall of peptic ulceration: A disease of civilization?
Authors: Roberts‐Thomson Ian C
Published: January 2018

Humans and Helicobacter pylori have evolved and adapted over tens of thousands of years. Yet peptic ulcer disease appeared to be rare prior to the 19th century. The prevalence of peptic ulcer disease increased between 1850 and 1900 and culminated in a cohort at high risk that was born at the end of the 19th century. This coincided with the provision of safe water and improvements in sanitation and personal hygiene. One hypothesis for the emergence of peptic ulcer disease focuses on the rate of development of atrophic gastritis induced by H. pylori. The hypothesis developed in this article focuses on delay in the age of acquisition of H. pylori to a time when immune and inflammatory responses to the infection were more mature. Whereas the acquisition of H. pylori in infancy usually resulted in mild pangastritis, hypochlorhydria, and a low risk for peptic ulcer disease, delayed acquisition could cause either more severe pangastritis (predisposing to gastric ulceration) or gastritis largely restricted to the antrum of the stomach (predisposing to duodenal ulceration). The decline in the prevalence of peptic ulcer disease over the past 100 years parallels the decline in the prevalence of H. pylori. The epidemic of ulcer disease in the first half of the 20th century seems likely to be an adverse effect of important public health measures undertaken in the latter half of the 19th century.
No Expiration Date on the Association Between Physical Activity and Mortality
Authors: Nicklas Barbara J.
Published: January 2018

This editorial comments on the article by LaMonte et al.
Parkinson's disease‐related DJ‐1 modulates the expression of uncoupling protein 4 against oxidative stress
Authors: Xu Shaoqing , Yang Xiaodong , Qian Yiwei , Xiao Qin
Published: January 2018

Loss of function mutations of DJ‐1 (PARK7) have been linked to the pathogenesis of Parkinson's disease. Antioxidative stress is one of the multi‐protective functions of DJ‐1, and oxidation of cysteine 106 has been proposed to regulate the protective activity of DJ‐1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH‐SY5Y) cells and DJ‐1 knockout mice to elucidate whether DJ‐1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism. The downstream products of oxidative stress, mitochondrial membrane potential (ΔΨm) and cell viability were also investigated. We found that UCP4 was up‐regulated upon 1‐methyl‐4‐phenylpyridinium (MPP+) stimulation in SH‐SY5Y cells, which was enhanced by wild type DJ‐1 and alleviated by DJ‐1 knockdown. Expression of UCP4 in DJ‐1 knockout mice was lower compared with wild‐type mice. In addition, up‐regulation of UCP4 was alleviated by inhibition of oxidized DJ‐1, and enhanced by increase in oxidized DJ‐1 under conditions of oxidative stress using western blot analysis. Moreover, over‐expression of UCP4 in DJ‐1 knockdown cells partially reversed the decrease in cell viability, ΔΨm, as well as the increase in products of oxidative stress upon MPP+ stimulation. Furthermore analysis showed that DJ‐1 regulated transcriptional activity of UCP4 partially via Nuclear factor‐kappa B (NF‐κB) pathway in the presence of MPP+. Together, our results suggested DJ‐1 might regulate the expression of UCP4 by oxidation of DJ‐1 and partially via NF‐κB pathway in its protective response to oxidative stress.

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Mathematical models of human cerebellar development in the fetal period
Authors: Dudek Krzysztof , Nowakowska‐Kotas Marta , Kędzia Alicja
Published: January 2018

The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown–rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non‐linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development.
Stereological analysis of individual lung lobes during normal and aberrant mouse lung alveolarisation
Authors: Hoang Tuong‐Van , Nardiello Claudio , Surate Solaligue David E. , Rodríguez‐Castillo José Alberto , Rath Philipp , Mayer Konstantin , Vadász István , Herold Susanne , Ahlbrecht Kathrin , Seeger Werner , Morty Rory E.
Published: January 2018

The quantitative assessment of the lung architecture forms the foundation of many studies on lung development and lung diseases, where parameters such as alveoli number, alveolar size, and septal thickness are quantitatively influenced by developmental or pathological processes. Given the pressing need for robust data that describe the lung structure, there is currently much enthusiasm for the development and refinement of methodological approaches for the unbiased assessment of lung structure with improved precision. The advent of stereological methods highlights one such approach. However, design‐based stereology is both expensive and time‐demanding. The objective of this study was to examine whether ‘limited’ stereological analysis, such as the stereological analysis of a single mouse lung lobe, may serve as a surrogate for studies on whole, intact mouse lungs; both in healthy lungs and in diseased lungs, using an experimental animal model of bronchopulmonary dysplasia (BPD). This served the dual‐function of exploring BPD pathobiology, asking whether there are regional (lobar) differences in the responses of developing mouse lungs to oxygen injury, by examining each mouse lung lobe separately in the BPD model. Hyperoxia exposure resulted in decreased alveolar density, alveoli number, and gas‐exchange surface area in all five mouse lung lobes, and increased the arithmetic mean septal thickness in all mouse lung lobes except the lobus cardialis. The data presented here suggest that – in healthy developing mice – a single mouse lung lobe might serve as a surrogate for studies on whole, intact mouse lungs. This is not the case for oxygen‐injured developing mouse lungs, where a single lobe would not be suitable as a surrogate for the whole, intact lung. Furthermore, as the total number of alveoli can only be determined by an analysis of the entire lung, and given regional differences in lung structure, particularly under pathological conditions, the stereological assessment of the whole, intact lung remains desirable.
Tail reduction process during human embryonic development
Authors: Tojima Sayaka , Makishima Haruyuki , Takakuwa Tetsuya , Yamada Shigehito
Published: January 2018

Although the human tail is completely absent at birth, the embryonic tail is formed just as in other tailed amniotes. Since all morphological variations are created from variations in developmental processes, elucidation of the tail reduction process during embryonic development may be necessary to clarify the human evolutionary process. The tail has also been of great interest to the medical community. The congenital anomaly referred to as ‘human tail’, i.e. the occurrence of a tail‐like structure, has been reported and was thought to represent a vestige of the embryonic tail; however, this hypothesis has not been verified. Accordingly, in this study, we aimed to establish a new method to visualize all somites in an embryo. We used sagittal‐sectioned embryos from Carnegie Stage (CS) 13 to CS23. All samples were obtained from the Congenital Anomaly Research Center, Kyoto University, Japan. Combining photomicroscopy and three‐dimensional reconstruction, we clearly visualized and labeled all somites. We found that the number of somites peaked at CS16 and dramatically decreased by approximately five somites. Tail reduction with a decrease in somites has also been observed in other short‐tailed amniotes; thus, this result suggested the possibility that there is a common mechanism for morphogenesis of short tails in amniote species. Additionally, our findings provided important insights into the cause of the congenital anomaly known as ‘human tail’.
Influence of body mass index on induction of labor: A historical cohort study
Authors: Dammer Ulf , Bogner Roswitha , Weiss Christel , Faschingbauer Florian , Pretscher Jutta , Beckmann Matthias W. , Sütterlin Marc , Kehl Sven
Published: January 2018

Aim

We aimed to determine the influence of body mass index (BMI) on induction of labor.

Methods

In this historical multicenter cohort study, 2122 labor inductions were analyzed. Women were divided into four groups according to their body mass index (BMI): BMI < 30 (normal group [NG]), 30 ≤ BMI < 35 (group 1 [G1]), 35 ≤ BMI < 40 (group 2 [G2]), and BMI ≥ 40 (group 3 [G3]). The primary outcome measure was the induction‐to‐delivery interval. The secondary outcome parameter was, among others, the rate of cesarean section.

Results

A total of 1113 inductions of labor were analyzed in the NG, 610 in G1, 239 in G2, and 160 in G3. The induction‐to‐delivery interval was shorter in the NG compared to G1 (mean values 1550 min vs 1669 min, P = 0.0406), G2 (1745 min, P = 0.0294), and G3 (1899 min, P = 0.0008). The cesarean section rate was significantly higher in G1–G3 (G1: 30.8%, P < 0.001; G2: 30.5%, P < 0.0067; G3: 42.5%, P < 0.0001) compared to the NG (21.8%). There were more vaginal deliveries within 48 h in the NG (84%) compared to G1–G3 (78%, P = 0.0186; 75%, P = 0.0049; 75%, P = 0.0329). However, these findings could mainly be seen in nulliparous women when stratifying for parity. Multivariable analysis showed that high BMI increased the induction‐to‐delivery interval whereas high parity, gestational age, and Bishop score decreased it.

Conclusion

An increased body mass index has a negative impact on induction of labor at term, especially in nulliparous women.
Effects of daytime versus night‐time cesarean deliveries on Stage II lactogenesis
Authors: İlhan Gülşah , Atmaca Fatma V. , Çümen Ayşenur , Zebitay Ali G. , Güngör Emre S. , Karasu Ayşe F. G.
Published: January 2018

Aim

The circadian timing system has a rhythm and one of the roles of this system is the mediation of hormonal and metabolic adaptations to lactation. This study was conducted to determine whether the time to stage II lactogenesis differed in women who underwent cesarean section (CS) in the daytime (DT) or night‐time (NT).

Methods

This study was conducted at Süleymaniye Research and Education Hospital between June and December 2016. Two hundred and eighty‐eight mothers who had a cesarean delivery and their healthy singleton neonates were included. Clinical and demographic data of the mothers and neonates, time of initiation of breastfeeding and time to stage II lactogenesis were analyzed according to DT or NT CS groups.

Results

There were no statistically significant differences in age, gravida, parity, body mass index, week of gestation at birth, postoperative hemoglobin level, cesarean indications, anesthesia type, previous history of breastfeeding, transfusion need, Apgar scores or birth weight‐height of neonates between the DT and NT CS groups. While the time of initiation of breastfeeding did not differ statistically in terms of DT or NT CS groups, the time to stage II lactogenesis was significantly longer in the NT CS group.

Conclusions

NT cesarean delivery is a risk factor for the delayed onset of lactogenesis. The results of this study may be useful to clinical practitioners counseling mothers who undergo NT cesarean delivery.
Salmonella serotypes isolated in geckos kept in seven collections in southern Italy
Authors: Russo T. P. , Varriale L. , Borrelli L. , Pace A. , Latronico M. , Menna L. F. , Fioretti A. , Dipineto L.
Published: January 2018

Objectives

Reptiles are considered an important reservoir of Salmonella species. This study evaluated the prevalence of Salmonella species in different species of gecko kept as pets in Italy.

Materials and Methods

Faecal swab samples were collected from 70 clinically healthy geckos and examined for Salmonella species by culture that were then serotyped.

Results

Salmonella species were isolated from 24 of 70 (34·3%) samples. Eighteen isolates expressed resistance to ceftazidime and four isolates to ampicillin.

Clinical Significance

Salmonella spp. can be isolated from apparently healthy captive gecko which should be considered as a potential source of infection for humans and other companion animals.
Development of a recombinant murine tumour model using hepatoma cells expressing hepatitis C virus nonstructural antigens
Authors: Young K. G. , Haq K. , MacLean S. , Dudani R. , Elahi S. M. , Gilbert R. , Weeratna R. D. , Krishnan L.
Published: January 2018

Hepatitis C virus (HCV) chronically infects 2%‐3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of relevant models to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing nonstructural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies. These HCV‐recombinant hepatoma cells formed large solid‐mass tumours when implanted into syngeneic mice, allowing us to test candidate HCV vaccines to demonstrate the development of an HCV‐specific immune response that limited tumour growth. Using this model, we tested the therapeutic potential of recombinant anti‐HCV‐specific vaccines based on two fundamentally different attenuated pathogen vaccine systems—attenuated Salmonella and recombinant adenoviral vector based vaccine. While attenuated Salmonella that secreted HCV antigens limited growth of the HCV‐recombinant tumours when used in a therapeutic vaccination trial, replication‐competent but noninfectious adenovirus expressing nonstructural HCV antigens showed overall greater survival and reduced weight loss compared to non‐replicating nondisseminating adenovirus. Our results demonstrate a model with anti‐tumour responses to HCV nonstructural (NS) protein antigens and suggest that recombinant vaccine vectors should be explored as a therapeutic strategy for controlling HCV and HCV‐associated cancers.
Role of cytochrome P450 2B sequence variation and gene copy number in facilitating dietary specialization in mammalian herbivores
Authors: Kitanovic Smiljka , Orr Teri J. , Spalink Daniel , Cocke Granger B. , Schramm Katharina , Wilderman P. Ross , Halpert James R. , Dearing M. Denise
Published: January 2018

Theory postulates that dietary specialization in mammalian herbivores is enabled by a specialized set of liver enzymes that process the high concentrations of similar plant secondary metabolites (PSMs) in the diets of specialists. To investigate whether qualitative and quantitative differences in detoxification mechanisms distinguish dietary specialists from generalists, we compared the sequence diversity and gene copy number of detoxification enzymes in two woodrat species: a generalist, the white‐throated woodrat (Neotoma albigula) and a juniper specialist, Stephens’ woodrat (N. stephensi). We focused on enzymes in the cytochrome P450 subfamily 2B (CYP2B), because previous research suggests this subfamily plays a key role in the processing of PSMs. For both woodrat species, we obtained and sequenced CYP2B cDNA, generated CYP2B phylogenies, estimated CYP2B gene copy number and created a homology model of the active site. We found that the specialist possessed on average ~5 more CYP2B gene copies than the generalist, but the specialist's CYP2B sequences were less diverse. Phylogenetic analysis of putative CYP2B homologs resolved woodrat species as reciprocally monophyletic and suggested evolutionary convergence of distinct homologs on similar key amino acid residues in both species. Homology modelling of the CYP2B enzyme suggests that interspecific differences in substrate preference and function likely result from amino acid differences in the enzyme active site. The characteristics of CYP2B in the specialist, that is greater gene copy number coupled with less sequence variation, are consistent with specialization to a narrow range of dietary toxins.
Bacterial outer membrane constriction
Authors: Egan Alexander J. F.
Published: January 2018

The outer membrane of Gram‐negative bacteria is a crucial permeability barrier allowing the cells to survive a myriad of toxic compounds, including many antibiotics. This innate form of antibiotic resistance is compounded by the evolution of more active mechanisms of resistance such as efflux pumps, reducing the already limited number of clinically relevant treatments for Gram‐negative pathogens. During cell division Gram‐negative bacteria must coordinate constriction of the outer membrane in conjunction with other crucial layers of the cell envelope, the peptidoglycan cell wall and the inner membrane. Coordination is crucial in maintaining structural integrity of the envelope, and represents a highly vulnerable time for the cell as any failure can be fatal, if not least disadvantageous. However, the molecular mechanisms of cell division and how the biogenesis of the three layers is synchronised during constriction remain largely unknown. Perturbations of the outer membrane have been shown to increase the effectiveness of antibiotics in vitro, and so with improved understanding of this process we may be able to exploit this vulnerability and improve the effectiveness of antibiotic treatments. In this review the current knowledge of how Gram‐negative bacteria facilitate constriction of their outer membranes during cell division will be discussed.
Aberrant accumulation of ErbB4 in progressive supranuclear palsy
Authors: Murakami A. , Nakamura M. , Kaneko S. , Lin W.‐L. , Dickson D. W. , Kusaka H.
Published: January 2018

Aims

The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1‐4). Neuregulin‐1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP).

Methods

The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis.

Results

Whereas C‐terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C‐terminal ErbB4 in PSP. Double immunofluorescence for C‐terminal ErbB4 and phospho‐tau revealed co‐localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N‐terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons.

Conclusions

Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.
Association between buccal mucosa ridging and oral or occlusal status among older people
Authors: Morita Koji , Mori Takahiro , Maruyama Mariko , Hiraoka Aya , Higa Chiaki , Kuroki Azusa , Yoshida Mitsuyoshi , Tsuga Kazuhiro
Published: January 2018

Objectives

This study aimed to evaluate the association between buccal mucosa ridging and oral or occlusal statuses among older people.

Subjects and Methods

This cross‐sectional study examined 262 independent older people (mean age, 74.2 ± 5.9 years) who participated in the Kyoto Elderly Physical Fitness Measurement Research Project. The predictor variables were oral statuses (number of present teeth and torus palatinus, torus mandibularis, temporomandibular joint noise, clenching, or grinding) and oral functions (occlusal pressure, cheek pressure, oral diadochokinesis, and tongue pressure). The outcome variable was the buccal mucosa ridging status (presence or absence). Additional variables were age, sex, body mass index, grip strength, and wearing dentures. We compared these variables between participants with and without buccal mucosa ridging using a univariate analysis and multiple logistic regression analysis.

Results

Buccal mucosa ridging was present in 177 (67.6%) people. Multiple logistic regression analysis revealed a close association of buccal mucosa ridging with torus mandibularis, tooth clenching and grinding and occlusal pressure, and cheek pressure.

Conclusions

Over 50% of the participants showed buccal mucosa ridging; this was significantly associated with higher cheek pressure, lower occlusal pressure, torus mandibularis, and tooth clenching and grinding.