bluuebunny/crossref_metadata_2025 huggingface dataset:
Roadmap of germline development and in vitro gametogenesis from pluripotent stem cells
Authors: Makar Karen , Sasaki Kotaro
Published: November 2019

Background

The germ cell lineage is a fundamental component of the metazoan life cycle, ensuring the perpetuation and substantial diversification of genetic information across generations. Recent advances in the understanding of mouse germ cell development have culminated in the ability to reconstitute gametogenesis in vitro, thereby enabling the biochemical and molecular analyses of germ cell specification and subsequent development in mice. Similar advances in reconstituting human germ cells in vitro would provide critical insight into the etiology of various reproductive conditions and disorders, including infertility.

Objectives

This review presents the mechanisms leading to germ cell development in mammals, particularly in mice and non‐human primates, as well as the applicability of these animal models to human germ cell development. The induction methods performed to recapitulate germ cell development in vitro are also discussed in this review, specifically focusing on in vitro gametogenesis from pluripotent stem cells.

Materials and methods

This review compiles the key methods and findings of various references relevant to the above‐mentioned topic.

Results

Murine models have provided essential mechanistic insight into the process of germ cell lineage development. However, there are several structural differences between mice and humans during early embryogenesis that hinder the extrapolation of findings made in murine models to what may occur in humans. Recent studies using human or non‐human primate embryos and human‐induced pluripotent stem cell (hiPSC)‐derived germ cells shed light on key cellular and genetic mechanisms governing germ cell development in humans.

Discussion

Utilizing the knowledge obtained from studying germ cell development in different animal models, induction methods established by various laboratories now permit partial reconstitution of human gametogenesis in vitro.

Conclusion

In vitro gametogenesis will constitute an emergent new field in human reproductive medicine in the near future, although legal and ethical considerations must be taken into account.
Historical Vignette: Attempted treatment of Sigmund Freud's oral squamous cell carcinoma by vasectomy (Steinach Operation) in 1923
Authors: Benmoussa Nadia , Charlier Philippe , Rebibo John‐David
Published: November 2019

Background

At the beginning of the 20th century, the Viennese physiologist Eugen Steinach proposed to treat the effects of physiological ageing by vasectomy. After experimenting his theory with animal, he published his results, and convinced scientists to apply this method to humans (ie men). The scientific community has been convinced by these pictures of the interest of these vasectomies, and many patients undergo it for the purpose of physical, mental and sexual rejuvenation, including Sigmund Freud.

Objectives

The aim of this study is to explain How Sigmund Freud decided to do this operation.

Materials and methods

We read and analysed a set of articles and books about Sigmund Freud live and the rejuvenation theory with the help of Sigmund Freud Museum (London).

Results

Freud suffered from a cancer of the right maxillary diagnosed in 1923 for which he underwent a first surgery of excision on April 20, 1923 followed by radiotherapy and a lot of another surgery to treat reccurences. Probably in despair or wanting to heal himself, he decided to have a Steinach vasectomy.

Discussion

Sigmund Freud knew Steinach's theories through his scientific publications, including his work on the «treatment of homosexuality» (sic!); he even tended to believe that biological methods were more reliable for «treating homosexuality» than his psychoanalyses. Because cancer was considered a disease of old age, vasectomy rejuvenation seemed to be useful (and potentially effective) in treating cancer, according to Freud.

Conclusion

Even Sigmund Freud, who was a great scientist, was fooled by the scientific results of a badly conducted study. We must keep a critical eye on new medical developments.
Hemi‐ablative low‐dose‐rate prostate brachytherapy for unilateral localised prostate cancer
Authors: Langley Stephen , Uribe Jennifer , Uribe‐Lewis Santiago , Franklin Adrian , Perna Carla , Horton Alex , Cunningham Melanie , Higgins Donna , Deering Claire , Khaksar Sara , Laing Robert
Published: November 2019

Objectives

To report clinical outcomes of the Hemi‐Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment‐related toxicity and effectiveness of hemi‐gland (HG) low‐dose‐rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer.

Patients and Methods

Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient‐reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole‐gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models.

Results

Pre‐treatment demography was similar between the 30 HG patients and 362 WG controls. Post‐implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post‐implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre‐treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post‐implant prostate‐specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32–67 months after implant.

Conclusion

This pilot study suggests that treatment‐related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.
Blockade of angiotensin AT1 receptors prevents arterial remodelling and stiffening in iron‐overloaded rats
Authors: Fidelis Helbert Gabriel , Mageski Jandinay Gonzaga Alexandre , Goes Susana Curry Evangelista , Botelho Tatiani , Marques Vinicius Bermond , Ávila Renata Andrade , dos Santos Leonardo
Published: November 2019

Background and Purpose

Damage to the vasculature caused by chronic iron‐overload in both humans and animal models, is characterized by endothelial dysfunction and reduced compliance. In vitro, blockade of the angiotensin II AT1 receptors reversed functional vascular changes induced by chronic iron‐overload. In this study, the effect of chronic AT1 receptor blockade on aorta stiffening was assessed in iron‐overloaded rats.

Experimental Approach

Male Wistar rats were treated for 15 days with saline as control group, iron dextran 200 mg·kg−1·day−1, 5 days a week (iron‐overload group), losartan (20 mg·kg−1·day−1 in drinking water), and iron dextran plus losartan. Mechanical properties of the aorta were assessed in vivo. In vitro, aortic geometry and biochemical composition were assessed with morphometric and histological methods.

Key Results

Thoracoabdominal aortic pulse wave velocity (PWV) increased significantly, indicating a decrease in aortic compliance. Co‐treatment with losartan prevented changes on PWV, β‐index, and elastic modulus in iron‐overloaded rats. This iron‐related increase in PWV was not related to changes in aortic geometry and wall stress. but to increased elastic modulus/wall stress ratio, suggesting that a change in the composition of the wall was responsible for the stiffness. Losartan treatment also ameliorated the increase in aorta collagen content of the iron‐overload group, without affecting circulating iron or vascular deposits.

Conclusions and Implications

Losartan prevented the structural and functional indices of aortic stiffness in iron‐overloaded rats, implying that inhibition of the renin–angiotensin system would limit the vascular remodelling in chronic iron‐overload.
G protein‐biased kratom‐alkaloids and synthetic carfentanil‐amide opioids as potential treatments for alcohol use disorder
Authors: Gutridge Anna M. , Robins Meridith T. , Cassell Robert J. , Uprety Rajendra , Mores Kendall L. , Ko Mee Jung , Pasternak Gavril W. , Majumdar Susruta , van Rijn Richard M.
Published: November 2019

Background and Purpose

Mitragyna speciosa, more commonly known as kratom, is a plant that contains opioidergic alkaloids but is unregulated in most countries. Kratom is used in the self‐medication of chronic pain and to reduce illicit and prescription opioid dependence. Kratom may be less dangerous than typical opioids because of the stronger preference of kratom alkaloids to induce receptor interaction with G proteins over β‐arrestin proteins. We hypothesized that kratom (alkaloids) can also reduce alcohol intake.

Experimental Approach

We pharmacologically characterized kratom extracts, kratom alkaloids (mitragynine, 7‐hydroxymitragynine, paynantheine, and speciogynine) and synthetic carfentanil‐amide opioids for their ability to interact with G proteins and β‐arrestin at μ, δ, and κ opioid receptors in vitro. We used C57BL/6 mice to assess to which degree these opioids could reduce alcohol intake and whether they had rewarding properties.

Key Results

Kratom alkaloids were strongly G protein‐biased at all three opioid receptors and reduced alcohol intake, but kratom and 7‐hydroxymitragynine were rewarding. Several results indicated a key role for δ opioid receptors, including that the synthetic carfentanil‐amide opioid MP102—a G protein‐biased agonist with modest selectivity for δ opioid receptors—reduced alcohol intake, whereas the G protein‐biased μ opioid agonist TRV130 did not.

Conclusion and Implications

Our results suggest that kratom extracts can decrease alcohol intake but still carry significant risk upon prolonged use. Development of more δ opioid‐selective synthetic opioids may provide a safer option than kratom to treat alcohol use disorder with fewer side effects.
X‐linked intellectual disability: Phenotypic expression in carrier females
Authors: Ziats Catherine A. , Schwartz Charles E. , Gecz Jozef , Shaw Marie , Field Michael J. , Stevenson Roger E. , Neri Giovanni
Published: November 2019

To better understand the landscape of female phenotypic expression in X‐linked intellectual disability (XLID), we surveyed the literature for female carriers of XLID gene alterations (n = 1098) and combined this with experience evaluating XLID kindreds at the Greenwood Genetic Center (n = 341) and at the University of Adelaide (n = 157). One‐hundred forty‐four XLID genes were grouped into nine categories based on the level of female phenotypic expression, ranging from no expression to female only expression. For each gene, the clinical presentation, gene expression in blood, X‐inactivation (XI) pattern, biological pathway involved, and whether the gene escapes XI were noted. Among the XLID conditions, 88 (61.1%) exhibited female cognitive phenotypic expression only, while 56 (38.9%) had no female phenotypic expression (n = 45), phenotype expression with normal cognition in females (n = 8), or unknown status for female phenotypic expression (n = 3). In twenty‐four (16.6%) XLID genes, XI was consistently skewed in female carriers, in 54 (37.5%) XI showed variable skewing, and in 33 (22.9%) XI was consistently random. The XI pattern was unknown in 33 (22.9%) XLID conditions. Therefore, there is evidence of a female carrier phenotype in the majority of XLID conditions although how exactly XI patterns influence the female phenotype in XLID conditions remains unclear.
From Third‐Class to World‐Class Citizens: Claiming Belonging, Countering Betrayal in the Margins of Ahmedabad
Authors: Salmi Jelena
Published: November 2019

This paper ethnographically explores the repercussions of the large‐scale displacement and resettlement of slum‐dwellers in the city of Ahmedabad, India, where state‐sponsored urban development aimed at the creation of a slum‐free world‐class city is strongly personified around the figure of Prime Minister Narendra Modi. Based on ten months’ fieldwork in the slum resettlement site of Sadbhavna Nagar in 2015–2016, I explore the intricacies of betrayal resulting from world‐class city making. First, I suggest that infrastructure interventions and futuristic imaginaries invoked dreams of a better future among the poor, but resulted in a sense of having been betrayed by both Modi and the state when people were physically and discursively excluded from the world‐class city. Second, I demonstrate how resettled people have engaged in micro‐level practices of betrayal by mobilizing middle‐class “nuisance talk” (Ghertner 2012) to denigrate their new, unwanted neighbors. I argue that the perceived betrayal by the state trickles down and translates into a betrayal of neighbors in the resettlement site, reinforcing the pre‐existing inequalities of caste and religion among the urban poor [Displacement; Urban Development; World‐Class City; Resettlement; India].
How can we correct for contingent valuation bias? A case study of the Macau Orchestra
Authors: Vinnicombe Thea , Sou Joey Pek U
Published: November 2019

The long‐standing contingent valuation method (CVM) is one of the most controversial techniques in economics. But it still remains the main means of assisting policymakers in understanding the preferences of ordinary citizens in valuing a range of non‐market goods believed to have positive external benefits. In the absence of viable alternatives, it is necessary that this method continues to be refined. This is especially important as CVM is increasingly being applied outside the area of environmental economics and outside the Western socio‐political context where theoretical advances have previously been made. This article examines three sources of bias in CVM in the context of valuing cultural goods: information, mixed good, and payment vehicle bias. A small case study of a publicly funded orchestra in an Asian city, the Macau Orchestra, is used to provide a preliminary exploration of the issues discussed.
An assessment of transesophageal echocardiography studies rated as rarely appropriate tests for infective endocarditis at an academic medical center
Authors: Amuchastegui Tomas , Hur David J. , Lynn Fillipon Nicole M. , Eder Maxwell D. , Bonomo Jason A. , Kim Yekaterina , McNamara Robert L. , Malinis Maricar , Sugeng Lissa
Published: November 2019

Purpose

Endocardial involvement documented by echocardiography is a major criterion of the modified Duke criteria (MDC) for infective endocarditis (IE). Though transesophageal echocardiography (TEE) is sensitive in the diagnosis of IE, it can be inappropriately used.

Methods

This retrospective study included all patients who underwent TEE due to bacteremia, fever, and/or endocarditis in a single, tertiary academic medical center in 2013. Data collected from electronic medical charts were as follows: demographics, history, physical examination, blood cultures, and transthoracic (TTE) and TEE findings. Cases were categorized based on appropriate use criteria (AUC) and MDC. An infectious disease (ID) specialist reviewed cases with rarely appropriate TEE use.

Results

In the 194 patients included, 147 (75.8%) were rated as appropriate, 36 (18.6%) rarely appropriate, and 11 (5.6%) uncertain. Of the 36 with rarely appropriate TEEs, using MDC 31 (86%) were rejected and 5 (14%) were possible for IE. Retrospective chart review by an ID specialist determined that 10 of these patients warranted TEE due to compelling issues, including immunosuppression or complicated infection.

Conclusions

In this retrospective cohort, almost one fifth of cases were rated as rarely appropriate. However, a review of these cases showed that TEE was often pursued when the clinical situation involved immunosuppression or complex infectious process. There remains room for improvement to our screening process for TEE and a need to implement a nuanced educational plan to better precisely identify appropriate cases for TEE usage.
Management of aortic valve replacement according to the gradient across symptomatic aortic valve stenosis and its prognostic impact
Authors: Bridonneau Valentin , Galli Elena , Auffret Vincent , Lederlin Mathieu , Campion Marine , Le Breton Herve , Boulmier Dominique , Hubert Arnaud , Lenz Pierre‐Axel , Leclercq Christophe , Oger Emmanuel , Donal Erwan
Published: November 2019

Background

Treatment strategy for low‐gradient (LG) aortic stenosis (AS) remains an unresolved issue. The presence of a low aortic gradient and preserved left ventricular ejection fraction (LVEF) might lead toward the underestimation of aortic stenosis severity and a more conservative management. We sought (a) to describe the nature and timing of intervention according to flow/gradient subgroups in patibents with LG‐AS, (2) to determine the factors associated with the decision to intervene, and (c) to describe prognosis.

Methods and Results

One hundred and ten patients prospectively included in this study underwent a standardized clinical and imaging evaluation at inclusion and at 1‐year follow‐up. According to aortic flow, gradient and LVEF, patients were divided into 4 groups: LG‐normal flow [n = 27], LG‐low flow‐low LVEF [n = 27], LG‐low flow‐normal LVEF [n = 16], and high gradient (HG) [n = 40]). 73% of patients underwent AVR 86 ± 59 days after the initial assessment. The HG subgroup had significantly higher intervention rates (P < .001). In multivariable analysis, four parameters were associated with the AVR: aortic gradient (HR 1.52 [1.10‐2.11], P = .012), LVEF (HR 0.58 [0.40‐0.85], P = .006), atrial fibrillation (HR 0.43 [0.021‐0.87], P = .019), and NT‐proBNP (HR 0.92[0.86‐0.98), P = .008]. Patients operated earlier had better outcomes than those having a delayed AVR (P = .042). LG‐AS patients had worse outcomes than HG‐AS patients (P < .001).

Conclusion

Compared to HG‐AS, LG‐AS is less likely to benefit from an AVR and had a significantly worse outcome. Further interventional studies are needed to investigate the timing of AVR in these patients.
Neural properties of fundamental function encoding of sound selectivity in the female avian auditory cortex
Authors: Inda Masahiro , Hotta Kohji , Oka Kotaro
Published: November 2019

Zebra finches (Taeniopygia guttata) use their voices for communication. Song structures in the songs of individual males are important for sound recognition in females. The caudomedial mesopallium (CMM) and nidopallium (NCM) are known to be essential higher auditory regions for sound recognition. These two regions have also been discussed with respect to their fundamental functions and song selectivity. To clarify their functions and selectivity, we investigated latencies and spiking patterns and also developed a novel correlation analysis to evaluate the relationship between neural activity and the characteristics of acoustic factors. We found that the latencies and spiking patterns in response to song stimuli differed between the CMM and NCM. In addition, our correlation analysis revealed that amplitude and frequency structures were important temporal acoustic factors for both regions. Although the CMM and NCM have different fundamental functions, they share similar encoding systems for acoustic factors.
Number of subjects required in common study designs for functional GABA magnetic resonance spectroscopy in the human brain at 3 Tesla
Authors: Sanaei Nezhad Faezeh , Lea‐Carnall Caroline A. , Anton Adriana , Jung JeYoung , Michou Emilia , Williams Stephen R. , Parkes Laura M.
Published: November 2019

Magnetic resonance spectroscopy (MRS) is a research tool for measuring the concentration of metabolites such as γ‐aminobutyric acid (GABA) and glutamate in the brain. MEGA‐PRESS has been the preferred pulse sequence for GABA measurements due to low physiological GABA concentrations, hence low signal. To compensate, researchers incorporate long acquisition durations (7–10 min) making functional measurements of this metabolite challenging. Here, the acquisition duration and sample sizes required to detect specific concentration changes in GABA using MEGA‐PRESS at 3 T are presented for both between‐groups and within‐session study designs. 75 spectra were acquired during rest using MEGA‐PRESS from 41 healthy volunteers in 6 different brain regions at 3 T with voxel sizes between 13 and 22 cm3. Between‐group and within‐session variance was calculated for different acquisition durations and power calculations were performed to determine the number of subjects required to detect a given percentage change in GABA/NAA signal ratio. Within‐subject variability was assessed by sampling different segments of a single acquisition. Power calculations suggest that detecting a 15% change in GABA using a 2 min acquisition and a 27 cm3 voxel size, depending on the region, requires between 8 and 93 subjects using a within‐session design. A between‐group design typically requires more participants to detect the same difference. In brain regions with suboptimal shimming, the subject numbers can be up to 4‐fold more. Collecting data for longer than 4 min in brain regions examined in this study is deemed unnecessary, as variance in the signal did not reduce further for longer durations.
Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats
Authors: Jefferys John G. R. , Arafat Muhammad A. , Irazoqui Pedro P. , Lovick Thelma A.
Published: November 2019

Objective

To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre‐Bötzinger complex, leading to sudden death.

Methods

Urethane‐anesthetized female Long‐Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus.

Results

Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre‐Bötzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty‐two of thirty‐one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas. Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse. Cardiac activity continued for tens of seconds.

Significance

Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP).
Comparison of outcomes following treatment of septic calcaneal bursitis by needle or bursoscopic lavage: A retrospective study of 29 horses
Authors: Duggan M. J. S. , Mair T. S.
Published: November 2019

Sepsis of the calcaneal bursae (CB) presents significant treatment challenges with limited clinical data available in the literature. The objective of this retrospective cohort study was to assess the clinical outcomes associated with CB lavage using either a through‐and‐through needle or bursoscopic technique. Clinical records of 29 horses treated for septic calcaneal bursitis using either technique between 2005 and 2019 were reviewed. Fisher’s exact test was used to assess statistical significance between first surgical technique and success at first surgery (i.e. not requiring >1 lavage), survival to discharge and return to work (RTW). Bursoscopy was performed in 13/29 (44.8%) cases, and needle lavage in 16/29 (55.2%). In the needle group, 12 (75%) horses were discharged following the first surgery. Four had repeat interventions; two (12.5%) had needle lavage and two (12.5%) had bursoscopy. Of the two horses to have repeat needle lavage, one was subjected to euthanasia and one discharged, and of the two that underwent bursoscopy, one was discharged and one received a third bursoscopy prior to discharge. In the bursoscopy group, seven (53.8%) were discharged and three (23.1%) were subjected to euthanasia following the first surgery. Three (23.1%) received a second bursoscopic lavage with one discharged, one subjected to euthanasia and one having a third bursoscopic lavage prior to discharge. Overall, 18/24 (75%) followed up cases RTW, 10 (55.5%) from the needle group, eight (44.4%) the bursoscopy group. No statistically significant differences between first surgical technique used and success at first surgery (no subsequent lavage(s) required), survival to discharge or return to work were detected. The main limitations of this study are that it is a retrospective study, has a small population with limited statistical power and potential selection bias. No statistically significant differences existed between the outcomes of the two techniques, contrary to the belief that bursoscopic lavage is superior. Larger, multicentred studies, with greater statistical power are required to further assess this relationship.
Aquifer Storage and Recovery Using Saline Aquifers: Hydrogeological Controls and Opportunities
Authors: Maliva Robert G. , Manahan William S. , Missimer Thomas M.
Published: November 2019

Aquifer storage and recovery (ASR) is a valuable tool for managing variations in the supply and demand of freshwater, but system performance is highly dependent upon system‐specific hydrogeological conditions including the salinity of the storage‐zone native groundwater. ASR systems using storage zones containing saline (>10,000 mg/L of total dissolved solids) groundwater tend to have relatively low recovery efficiencies (REs). However, the drawbacks of low REs may be offset by lesser treatment requirements and may be of secondary importance where the stored water (e.g., excess reclaimed, surface, and storm waters) would otherwise go to waste and pose disposal costs. Density‐dependent, solute‐transport modeling results demonstrate that the RE of ASR systems using a saline storage zone is most strongly controlled by parameters controlling free convection (e.g., horizontal hydraulic conductivity) and mixing of recharged and native groundwater (e.g., dispersivity and aquifer heterogeneity). Preferred storage zone conditions are moderate hydraulic conductivities (5 to 20 m/d), low degrees of aquifer heterogeneity, and primary porosity‐dominated siliclastic and limestones lithologies with effective porosities greater than 5%. Where hydrogeological conditions are less favorable, operational options are available to improve RE, such as preferential recovery from the top of the storage zone. Injection of large volumes of excess water currently not needed into saline aquifers could create valuable water resources that could be tapped in the future during times of greater need.
Thermal and crystallization kinetics of yttrium‐doped phosphate‐based glasses
Authors: Arafat Abul , Samad Sabrin A. , Wadge Matthew D. , Islam Md Towhidul , Lewis Andrew L. , Barney Emma R. , Ahmed Ifty
Published: November 2019

Yttrium‐doped glasses have been utilized for biomedical applications such as radiotherapy, especially for liver cancer treatment. In this paper, the crystallization behavior of phosphate‐based glasses doped with yttrium (in the system 45P2O5–(30 − x) Na2O–25CaO–xY2O3—where x = 0, 1, 3 and 5) have been investigated via Differential Scanning Calorimetry (DSC) using nonisothermal technique at different heating rates (5°C, 10°C, 15°C and 20°C/min). The glass compositions were characterized via EDX, XRD, Density and Molar volume analysis. The Moynihan and Kissinger methods were used for the determination of glass transition activation energy (Eg) which decreased from 192 to 118 kJ/mol (Moynihan) and 183 to 113 kJ/mol (Kissinger) with increasing yttrium oxide content. Incorporation of 0 to 5 mol% Y2O3 revealed an approximate decrease of 71 kJ/mol (Ozawa and Augis) for onset crystallization (Ex) and 26 kJ/mol (Kissinger) for crystallization peak activation energies (Ec). Avrami index (n) value analyzed via Matusita–Sakka equation suggested a one‐dimensional crystal growth for the glasses investigated. SEM analysis explored the crystalline morphologies and revealed one‐dimensional needle‐like crystals. Overall, it was found that these glass formulations remained amorphous with up to 5 mol% Y2O3 addition with further increases in Y2O3 content resulting in significant crystallization.
Camel milk regulates T‐cell proliferation to alleviate dextran sodium sulphate‐induced colitis in mice
Authors: Cui Changwan , Lu Yiping , Yue Yuanyi , Wu Si , Wang Shuang , Yu Miao , Sun Zhengrong
Published: November 2019

The incidence of inflammatory bowel disease (IBD) is increasing in China. Current clinical methods of treatment for IBD are accompanied by side effects, and thus, the search for effective therapeutic drugs with minimal adverse effects is necessary. In the present study, the effects of camel milk (CM) on dextran sodium sulphate (DSS)‐induced acute and chronic colitis in a mouse model were investigated. The results showed CM effectively alleviated the injury induced by DSS to the colon mucosa and imbalance of immune cells in mice. However, treatment with CM significantly increased the body weight of mice and decreased the disease activity index (DAI), histopathological score, proliferation of Th17 cells and concentration of inflammatory cytokine IL‐17. The results from the present study indicate CM possesses intestinal protective effects.
Production and characterisation of antioxidant peptides from sweet potato protein by enzymatic hydrolysis with radio frequency pretreatment
Authors: Zhang Miao , Huang Tung‐Shi , Mu Tai‐Hua
Published: November 2019

Effect of radio frequency (RF at 70, 80 and 90 °C) pretreatment on production and characterisation of sweet potato protein hydrolysates (SPPH) prepared using Alcalase (ALC), Protease (PRO) and the combination of ALC + PRO was investigated. RF highly improved degree of hydrolysis (DH) and enhanced antioxidant activity of all SPPH produced by ALC, PRO and the combination as compared to traditional water bath (WB) heating pretreatment (P < 0.05). RF significantly increased molecular weight (MW) <3 kDa peptide fraction from SPPH produced by ALC, and MW <3 kDa peptide fraction from RF80‐ and RF90‐pretreated samples has higher antioxidant activity. Diverse peptides in MW <3 kDa fractions with RF80 and RF90 pretreatments were identified using LC–QTOF–MS/MS, which matched the sequences of sporamins and contained antioxidant amino acids Trp, Tyr, Met, Phe and/or His. There is a great potential application of using SPPH in functional foods as a novel ingredient.
Analysis of flavour compounds and prediction of sensory properties in sea buckthorn (Hippophaë rhamnoides L.) berries
Authors: Ma Xueying , Yang Wei , Marsol‐Vall Alexis , Laaksonen Oskar , Yang Baoru
Published: November 2019

The aim of this study was to investigate sugars, organic acids, flavonol glycosides (FGs), proanthocyanidins and volatiles as flavour compounds in sea buckthorn (SB) berries of five cultivars and to predict the sensory properties of berries. The profiles of flavour compounds in SB berries varied significantly among the cultivars. Total proanthocyanidins and FGs were highest in ‘Pertsik’ and ‘Raisa’, respectively. Total volatiles were highest in ‘Vorobyevskaya’ and lowest in ‘Raisa’. A previously established PLS model was used to predict the sensory properties of SB berries based on the non‐volatile flavour compounds. The mouth‐drying astringency can be predicted the most reliably, which has the highest regression coefficients with quinic acid, isorhamnetin‐3‐O‐sophoroside‐7‐O‐rhamnoside and total proanthocyanidins. Bitterness cannot be predicted using the model. ‘Pertsik’ berries were predicted to be more mouth‐drying astringency and sour than those of ‘Raisa’. The research supports the cultivar selection in cultivation and industry of SB berries.
Red meat (beef and sheep) products for an ageing population: a review
Authors: Holman Benjamin W.B. , Fowler Stephanie M. , Hopkins David L.
Published: November 2019

The global population is becoming older, and still, this cohort considers red meat (beef and sheep meat) as an important staple in their diet. It is understood that the requirements from these red meats will vary as a person ages, often because of associated physiological changes; nutrition and health concerns; and reduced sensorial capacities. This creates an imperative to develop red meat products that appeal and satisfy the demands of elderly people. Here, we have reviewed current literature with the aim to comprehend the elderly consumer market, their demands for nutritive and quality traits, and their requirements for safe and convenient red meat (beef and sheep) products. Based on these studies, it was apparent that these specifications may be delivered using available knowledge of intrinsic and extrinsic influences on red meat if considered within the context of elderly customers, that is, to deliver upon elderly people’s requirements for conventional red meat products which are inexpensive, of consistent and perceivable high quality, and quell any associated health concerns for the consumer.
Modeling birefringence in SiO2 glass fiber using surface stress relaxation
Authors: Hausmann Bronson D. , Miller Paul A. , Aaldenberg Emily M. , Blanchet Thierry A. , Tomozawa Minoru
Published: November 2019

The retardance of silica glass fibers was evaluated using photoelastic techniques. Here, surface birefringence in glass fibers is shown to be a consequence of surface stress relaxation for as‐received fibers drawn from Suprasil II. The surface features of the birefringent fibers were compared to a model of the residual axial stress profile resulting from a diffusion‐controlled surface stress relaxation. Additionally, a uniform birefringence in the fiber equivalent to a constant tensile stress was recognized and attributed to structural anisotropy produced during fiber drawing. The contribution of structural anisotropy to the observed birefringence remained constant as the surface features were successively etched away. Surface compressive stress generation was also observed, as retardance corresponding to a surface compressive stress was found to increase with applied tensile stress during short heat treatments. Significant features of the retardance profile in as‐received silica glass fibers, with a thin surface compressive stress layer and compensating interior tensile stress, agreed with the residual stress profiles predicted by the surface stress relaxation model after correcting for this observed structural anisotropy.
y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: Implications in the pathophysiology of Lysinuric Protein Intolerance
Authors: Rotoli Bianca Maria , Barilli Amelia , Visigalli Rossana , Ferrari Francesca , Dall’Asta Valeria
Published: November 2019

y+LAT1 (encoded by SLC7A7), together with y+LAT2 (encoded by SLC7A6), is the alternative light subunits composing the heterodimeric transport system y+L for cationic and neutral amino acids. SLC7A7 mutations cause lysinuric protein intolerance (LPI), an inherited multisystem disease characterized by low plasma levels of arginine and lysine, protein‐rich food intolerance, failure to thrive, hepatosplenomegaly, osteoporosis, lung involvement, kidney failure, haematologic and immunological disorders. The reason for the heterogeneity of LPI symptoms is thus far only poorly understood. Here, we aimed to quantitatively compare the expression of SLC7A7 and SLC7A6 among different human cell types and evaluate y+LAT1 and y+LAT2 contribution to arginine transport. We demonstrate that system y+L‐mediated arginine transport is mainly accounted for by y+LAT1 in monocyte‐derived macrophages (MDM) and y+LAT2 in fibroblasts. The kinetic analysis of arginine transport indicates that y+LAT1 and y+LAT2 share a comparable affinity for the substrate. Differences have been highlighted in the expression of SLC7A6 and SLC7A7 mRNA among different cell models: while SLC7A6 is almost equally expressed, SLC7A7 is particularly abundant in MDM, intestinal Caco‐2 cells and human renal proximal tubular epithelial cells (HRPTEpC). The characterization of arginine uptake demonstrates that system y+L is operative in renal cells and in Caco‐2 where, at the basolateral side, it mediates arginine efflux in exchange with leucine plus sodium. These findings explain the defective absorption/reabsorption of arginine in LPI. Moreover, y+LAT1 is the prevailing transporter in MDM sustaining a pivotal role in the pathogenesis of immunological complications associated with the disease.
Family history of diabetes in both parents is strongly associated with impaired residual β‐cell function in Japanese type 2 diabetes patients
Authors: Iwata Minoru , Kamura Yutaka , Honoki Hisae , Kobayashi Kaori , Ishiki Manabu , Yagi Kunimasa , Fukushima Yasuo , Takano Atsuko , Kato Hiromi , Murakami Shihou , Higuchi Kiyohiro , Kobashi Chikaaki , Fukuda Kazuhito , Koshimizu Yukiko , Tobe Kazuyuki
Published: November 2019

Aims/Introduction

The objective of the present study was to clarify the association of the type and number of first‐degree family history of diabetes (FHD) with the clinical characteristics, especially with residual β‐cell function, in type 2 diabetes patients.

Materials and Methods

A total of 1,131 type 2 diabetes patients were recruited and divided into four groups according to FHD information as follows: (i) patients without FHD (FHD−); (ii) those with at least one sibling who had diabetes without parental diabetes (FHD+); (iii) those with one parent (FHD++); or (iv) those with both parents (FHD+++) who had diabetes with or without a sibling with diabetes.

Results

The percentages of the FHD−, FHD+, FHD++ and FHD+++ groups were 49.4%, 13.4%, 34.0% and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P < 0.001) than those in the FHD− and FHD+ groups, even after adjusting for confounding factors. In addition, the levels of insulin secretion were significantly lower in the patients in the FHD+, FHD++ and FHD+++ groups than those in the FHD− group (P < 0.05) after adjusting for confounding factors, and the patients in the FHD+++ group presented with the lowest levels of insulin secretion among the four groups.

Conclusions

Our results showed that in type 2 diabetes patients, the degree of the associations between FHD and clinical characteristics differs according to the number and the type of FHD. In particular, FHD in both parents is most strongly associated with impaired residual β‐cell function.
Differential response to larval crowding of a long‐ and a short‐lived medfly biotype
Authors: Diamantidis Alexandros D. , Ioannou Charalampos S. , Nakas Christos T. , Carey James R. , Papadopoulos Nikos T.
Published: November 2019

Response of endophytic fruit fly species (Tephritidae) to larval crowding is a form of scramble competition that may affect important life history traits of adults, such as survival and reproduction. Recent empirical evidence demonstrates large differences in adult life history traits, especially longevity, among Mediterranean fruit fly (Ceratitis capitata;"medfly") biotypes obtained from different regions of the world. However, whether the evolution of long lifespan is associated with response to stress induced by larval crowding has not been fully elucidated. We investigated, under constant laboratory conditions, the response of a short‐ and a long‐lived medfly biotypes to stress induced by larval crowding. Survival and development of larvae and pupae and the size of resulting pupae were recorded. The lifespan and age‐specific egg production patterns of the obtained adults were recorded. Our findings reveal that increased larval density reduced immature survival (larvae and pupae) in the short‐lived biotype but had rather neutral effects on the longed‐lived one. Only larvae of the long‐lived biotype were capable of prolonging their developmental duration under the highest crowding regime to successfully pupate and emerge as adults. Response of emerging adults to larvae crowding conditions was similar in the two medfly biotypes. Those individuals emerging from high larval density regimes had reduced longevity and fecundity. Long‐lived biotype individuals, however, appeared to suffer a higher cost in longevity compared with the short‐lived one. The importance of our findings to understand the evolution of long lifespan is discussed.
Innate responses to conspecific and heterospecific alarm cues in the endangered eastern cape redfin Pseudobarbus afer
Authors: Magellan Kit , Booth Anthony J. , Weyl Olaf L. F.
Published: November 2019

We examined innate responses to conspecific and heterospecific alarm cues in a small cyprinid minnow, the Eastern Cape redfin Pseudobarbus afer. We found that redfins respond to conspecific skin extract, which contains alarm chemicals, and showed that their preferred response is to hide in refugia. Redfins also respond to skin extract from an allopatric, distantly related minnow species, the chubbyhead barb Enteromius anoplus indicating that neither sympatry nor close phylogenetic relationships are necessary for recognition of heterospecific alarm cues. Although both conspecific and heterospecific alarm cues induced similar responses, the response to heterospecific cues was less intense. This may be explained by a trade‐off between selection to maximise threat recognition and selection to avoid the costs of responding to irrelevant cues, or by differences in chemical structures of alarm cues between species. These findings have implications for the conservation of this Endangered fish species and for freshwater fishes throughout Africa.
Microtubule‐dependent processes precede pathological calcium influx in excitotoxin‐induced axon degeneration
Authors: Tian Nan , Hanson Kelsey A. , Canty Alison J. , Vickers James C. , King Anna E.
Published: November 2019

Axon degeneration and axonal loss is a feature of neurodegenerative disease and injury and occurs via programmed pathways that are distinct from cell death pathways. While the pathways of axonal loss following axon severing are well described, less is known about axonal loss following other neurodegenerative insults. Here we use primary mouse cortical neuron cultures grown in compartmentalized chambers to investigate the role of calcium in the degeneration of axons that occurs following a somal insult by the excitotoxin kainic acid. Calcium influx has been implicated in both excitotoxicity and axon degeneration mechanisms, however the link between a somal insult and axonal calcium increase is unclear. Live imaging of axons demonstrated that pharmacologically preventing intracellular calcium increases through the endoplasmic reticulum or mitochondria significantly (p < 0.05) reduced axon degeneration. Live calcium‐imaging with the Ca2+ indicator Fluo‐4 demonstrated that kainic acid exposure to the soma resulted in a rapid, and transient, increase in calcium in the axon, which occured even at low kainic acid concentrations that do not cause axon degeneration within 24 h. However, this calcium transient was followed by a gradual increase in axonal calcium, which was associated with axonal loss. Furthermore, treatment with a range of doses of the microtubule stabilizing drug taxol, which protects against axon fragmentation in this model, prevented this gradual calcium increase, suggesting that the intra‐axonal calcium changes are downstream of microtubule associated events. Biochemical analysis of taxol treated neurons demonstrated a shift in microtubule post‐translational modifications, with a significant (p < 0.05) increase in acetylated tubulin and a significant (p < 0.05) decrease in tyrosinated tubulin, suggestive of a more stable microtubule pool. Together our results suggest that axonal degeneration following excitotoxicity is dependent on an increase in axonal calcium, which is downstream of a microtubule‐dependent event.

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Involvement of homodomain interacting protein kinase 2‐c‐Jun N‐terminal kinase/c‐Jun cascade in the long‐term synaptic toxicity and cognition impairment induced by neonatal Sevoflurane exposure
Authors: Liang Lirong , Xie Rougang , Lu Rui , Ma Ruixue , Wang Xiaoxia , Wang Fengjuan , Liu Bing , Wu Shengxi , Wang Yazhou , Zhang Hui
Published: November 2019

Sevoflurane is one of the most widely used anesthetics with recent concerns rising about its pediatric application. The synaptic toxicity and mechanisms underlying its long‐term cognition impairment remain unclear. In this study, we investigated the expression and roles of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neuronal survival and synaptic plasticity, and its downstream c‐Jun N‐terminal kinase (JNK)/c‐Jun signaling in the long‐term toxicity of neonatal Sevoflurane exposure. Our data showed that neonatal Sevoflurane exposure results in impairment of memory, enhancement of anxiety, less number of excitatory synapses and lower levels of synaptic proteins in the hippocampus of adult rats without significant changes of hippocampal neuron numbers. Up‐regulation of HIPK2 and JNK/c‐Jun was observed in hippocampal granular neurons shortly after Sevoflurane exposure and persisted to adult. 5‐((6‐Oxo‐5‐(6‐(piperazin‐1‐yl)pyridin‐3‐yl)‐1,6‐dihydropyridin‐3‐yl)methylene)thiazolidine‐2,4‐dione trifluoroacetate, antagonist of HIPK2, could significantly rescue the cognition impairment, decrease in long‐term potentiation, reduction in spine density and activation of JNK/c‐Jun induced by Sevoflurane. JNK antagonist SP600125 partially restored synapse development and cognitive function without affecting the expression of HIPK2. These data, in together, revealed a novel role of HIPK2‐JNK/c‐Jun signaling in the long‐term synaptic toxicity and cognition impairment of neonatal Sevoflurane exposure, indicating HIPK2‐JNK/c‐Jun cascade as a potential target for reducing the synaptic toxicity of Sevoflurane.

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Cover Image for this issue: doi: 10.1111/jnc.14757.