bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function
Authors: Rivera Bastián , Moreno Claudio , Lavanderos Boris , Hwang Ji Yeon , Fernández-Trillo Jorge , Park Kang-Sik , Orio Patricio , Viana Félix , Madrid Rodolfo , Pertusa María 
Published: August 2021

In mammals, environmental cold sensing conducted by peripheral cold thermoreceptor neurons mostly depends on TRPM8, an ion channel that has evolved to become the main molecular cold transducer. This TRP channel is activated by cold, cooling compounds, such as menthol, voltage, and rises in osmolality. TRPM8 function is regulated by kinase activity that phosphorylates the channel under resting conditions. However, which specific residues, how this post-translational modification modulates TRPM8 activity, and its influence on cold sensing are still poorly understood. By mass spectrometry, we identified four serine residues within the N-terminus (S26, S29, S541, and S542) constitutively phosphorylated in the mouse ortholog. TRPM8 function was examined by Ca2+imaging and patch-clamp recordings, revealing that treatment with staurosporine, a kinase inhibitor, augmented its cold- and menthol-evoked responses. S29A mutation is sufficient to increase TRPM8 activity, suggesting that phosphorylation of this residue is a central molecular determinant of this negative regulation. Biophysical and total internal reflection fluorescence-based analysis revealed a dual mechanism in the potentiated responses of unphosphorylated TRPM8: a shift in the voltage activation curve toward more negative potentials and an increase in the number of active channels at the plasma membrane. Importantly, basal kinase activity negatively modulates TRPM8 function at cold thermoreceptors from male and female mice, an observation accounted for by mathematical modeling. Overall, our findings suggest that cold temperature detection could be rapidly and reversibly fine-tuned by controlling the TRPM8 basal phosphorylation state, a mechanism that acts as a dynamic molecular brake of this thermo-TRP channel function in primary sensory neurons.SIGNIFICANCE STATEMENTPost-translational modifications are one of the main molecular mechanisms involved in adjusting the sensitivity of sensory ion channels to changing environmental conditions. Here we show, for the first time, that constitutive phosphorylation of the well-conserved serine 29 within the N-terminal domain negatively modulates TRPM8 channel activity, reducing its activation by agonists and decreasing the number of active channels at the plasma membrane. Basal phosphorylation of TRPM8 acts as a key regulator of its function as the main cold-transduction channel, significantly contributing to the net response of primary sensory neurons to temperature reductions. This reversible and dynamic modulatory mechanism opens new opportunities to regulate TRPM8 function in pathologic conditions where this thermo-TRP channel plays a critical role.
Optogenetic Activation of V1 Interneurons Reveals the Multimodality of Spinal Locomotor Networks in the Neonatal Mouse
Authors: Falgairolle Melanie , O'Donovan Michael J. 
Published: August 2021

In the spinal cord, classes of interneurons have been studiedin vitroto determine their role in producing or regulating locomotion. It is unclear whether all locomotor behaviors are produced by the same circuitry or engage different subsets of neurons. Here, in neonatal mice of either sex, we test this idea by comparing the actions of a class of spinal, inhibitory interneuron (V1) expressing channelrhodopsin driven by theengrailed-1transcription factor on the rhythms elicited by different methods. We find that, although the overall locomotor activitiesin vitroare similar, V1 interneuron depolarization produces opposite effects depending of the mode of activation of the locomotor circuitry. The differential behavior of V1 neurons suggests that their function depends on how the locomotor rhythm is activated and is consistent with the idea that the functional organization of the corresponding locomotor networks also differs.SIGNIFICANCE STATEMENTThe neural networks dictating the execution of fictive locomotion are located in the spinal cord. It is generally assumed that the mode of activation of these spinal networks should not change the recruitment or function of neurons. Here, we manipulated the activity of a class of interneuron (V1), which targets these networks and found that their activation induces opposite effects depending on the mode of activation. This suggests that the mode of activation of the spinal networks differentially recruits either V1 interneurons or other interneurons, or both.
Restoring the Molecular Clockwork within the Suprachiasmatic Hypothalamus of an Otherwise Clockless Mouse Enables Circadian Phasing and Stabilization of Sleep-Wake Cycles and Reverses Memory Deficits
Authors: Maywood Elizabeth S. , Chesham Johanna E. , Winsky-Sommerer Raphaelle , Hastings Michael H. 
Published: August 2021

The timing and quality of sleep-wake cycles are regulated by interacting circadian and homeostatic mechanisms. Although the suprachiasmatic nucleus (SCN) is the principal clock, circadian clocks are active across the brain and the respective sleep-regulatory roles of SCN and local clocks are unclear. To determine the specific contribution(s) of the SCN, we used virally mediated genetic complementation, expressing Cryptochrome1 (Cry1) to establish circadian molecular competence in the suprachiasmatic hypothalamus of globally clockless, arrhythmic maleCry1/Cry2-null mice. Under free-running conditions, the rest/activity behavior ofCry1/Cry2-null controls expressing EGFP (SCNCon) was arrhythmic, whereas Cry1-complemented mice (SCNCry1) had coherent circadian behavior, comparable to that of Cry1,2-competent wild types (WTs). In SCNConmice, sleep-wakefulness, assessed by electroencephalography (EEG)/electromyography (EMG), lacked circadian organization. In SCNCry1mice, however, it matched WTs, with consolidated vigilance states [wake, rapid eye movement sleep (REMS) and non-REMS (NREMS)] and rhythms in NREMS δ power and expression of REMS within total sleep (TS). Wakefulness in SCNConmice was more fragmented than in WTs, with more wake-NREMS-wake transitions. This disruption was reversed in SCNCry1mice. Following sleep deprivation (SD), all mice showed a homeostatic increase in NREMS δ power, although the SCNConmice had reduced NREMS during the inactive (light) phase of recovery. In contrast, the dynamics of homeostatic responses in the SCNCry1mice were comparable to WTs. Finally, SCNConmice exhibited poor sleep-dependent memory but this was corrected in SCNCry1mice. In clockless mice, circadian molecular competence focused solely on the SCN rescued the architecture and consolidation of sleep-wake and sleep-dependent memory, highlighting its dominant role in timing sleep.SIGNIFICANCE STATEMENTThe circadian timing system regulates sleep-wake cycles. The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian clock, but the presence of multiple local brain and peripheral clocks mean the respective roles of SCN and other clocks in regulating sleep are unclear. We therefore used virally mediated genetic complementation to restore molecular circadian functions in the suprachiasmatic hypothalamus, focusing on the SCN, in otherwise genetically clockless, arrhythmic mice. This initiated circadian activity-rest cycles, and circadian sleep-wake cycles, circadian patterning to the intensity of non-rapid eye movement sleep (NREMS) and circadian control of REMS as a proportion of total sleep (TS). Consolidation of sleep-wake established normal dynamics of sleep homeostasis and enhanced sleep-dependent memory. Thus, the suprachiasmatic hypothalamus, alone, can direct circadian regulation of sleep-wake.
Maternal Vaccination and Infant Influenza and Pertussis
Authors: Rowe Stacey L. , Leder Karin , Perrett Kirsten P. , Romero Nicole , Nolan Terry M. , Stephens Nicola , Cowie Benjamin C. , Cheng Allen C. 
Published: August 2021

BACKGROUND AND OBJECTIVES
Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants.

METHODS
This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged &lt;2 months, 2 to &lt;6 months, and &lt;6 months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%.

RESULTS
Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged &lt;2 months and 35.7% (2.2% to 57.7%) for infants aged 2 to &lt;6 months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged &lt;2 months and 31.8% (95% CI, −39.1% to 66.6%) for infants aged 2 to &lt;6 months.

CONCLUSIONS
Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged &lt;2 months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.
LAS ECONOMÍAS COLABORATIVAS EN TURISMO, ¿UNA RESPUESTA DE DESARROLLO ECONÓMICO SOSTENIBLE? CASO ALOJAMIENTOS CIUDAD DE MEDELLÍN
Authors: Larrea David Luisa 
Published: August 2021

El fenómeno de las economías colaborativas es un tema que ha causado controversia en todo el mundo; la economía colaborativa se ha popularizado en sectores relacionados con el turismo como el transporte y el alojamiento. Este estudio empresarial cuyo objetivo fue el de analizar la contribución de las economías colaborativas en alojamiento al desarrollo económico sostenible de los territorios.
Para los fines de esta investigación, se diseñó un modelo metodológico mixto, apoyado en instrumentos cualitativos como la entrevista, observación y revisión bibliográfica, e instrumentos como la encuesta a empresarios turísticos tradicionales. La aplicación de la metodología permitió conocer los cambios que ha experimentado el alojamiento tradicional en la zona de Laureles-Estadio de la comuna 11 en Medellín; estos cambios están principalmente relacionados con el acceso al mercado, así como con una de las principales preocupaciones de los empresarios de alojamiento tradicional, la regulación empresarial turística del país que hasta ahora no se tiene en cuenta para las empresas colaborativas. Si se quiere promover un ambiente donde ambos tipos de alojamiento puedan relacionarse en el mercado mediante una convivencia empresarial, el primer paso debe ser que el sector público genere una regulación que tenga en cuenta las necesidades y particularidades de ambos, así como la igualdad en las condiciones que se establecen para la operación del servicio de alojamiento.
Different Classical Methods of Estimation and Chi-squared Goodness-of-fit Test for Unit Generalized Inverse Weibull Distribution
Authors: Aidi khaoula  , Sanku Dey  , Kumar Devendra , Seddik-Ameur N  
Published: August 2021

In this paper, we try to contribute to the distribution theory literature by incorporating a new bounded distribution, called the unit generalized inverse Weibull distribution (UGIWD) in the (0, 1) intervals by transformation method. The proposed distribution exhibits increasing and bathtub shaped hazard rate function. We derive some basic statistical properties of the new distribution. Based on complete sample, the model parameters are obtained by the methods of maximum likelihood, least square, weighted least square, percentile, maximum product of spacing and Cram`er-von-Mises and compared them using Monte Carlo simulation study. In addition, bootstrap confidence intervals of the parameters of the model based on aforementioned methods of estimation are also obtained. We illustrate the performance of the proposed distribution by means of one real data set and the data set shows that the new distribution is more appropriate as compared to unit Birnbaum-Saunders, unit gamma, unit Weibull, Kumaraswamy and unit Burr III distributions. Further, we construct chi-squared goodness-of-fit tests for the UGIWD using right censored data based on Nikulin-Rao-Robson (NRR) statistic and its modification. The criterion test used is the modified chi-squared statistic Y^2, developedby Bagdonavi?ius and Nikulin, 2011 for some parametric models when data are censored. The performances of the proposed test are shown by an intensive simulation study and an application to real data set
Dampak Pemberian Mikroenkapsulasi Minyak Ikan dalam Pakan terhadap Kolesterol Darah dan Performa pada Domba
Authors: Riemas Ganesha Ade , Hernaman Iman , Ramdani Diky , Nurhadi Bambang 
Published: August 2021

ABSTRAK. Tujuan penelitian ini untuk mengukur seberapa besar pengaruh minyak ikan yang sudah terenkapsulasi terhadap kolesterol darah dan performa pada Domba. Penelitian telah dilakukan di Sub Unit Pelayanan Pengembangan Pembibitan Ternak Domba dan Kambing (SUPPPTDK) Bunihayu, Subang pada tanggal 20 Januari 2020 sampai 27 Maret 2020. Sebanyak 18 ekor domba Ekor Tipis jantan dengan bobot 15,99±0,98 kg dialokasikan ke dalam 3 perlakuan secara acak. Domba tersebut diberi ransum perlakuan yang disuplementasi dengan mikroenkapsulasi minyak ikan sebanyak 0% (P0), 2,5% (P1), dan 5% (P2). Data yang terkumpul dilakukan analisis ragam dan bila hasil berbeda nyata maka dilanjutkan dengan uji Duncan. Hasil menunjukkan bahwa mikroenkapsulasi minyak ikan dapat menurunkan kolesterol darah (P0,05), namun tidak berpengaruh nyata terhadap pertambahan bobot badan, konsumsi dan konversi ransum (P0,05). Penurunan kadar kolesterol terjadi pada kelompok domba dengan perlakuan mikroenkapsulasi sebanyak 2,5% (P1) dan mikroenkapsulasi 5% (P2). Kadar kolesterol darah masing-masing perlakuan berturut-turut adalah 100,70 mg/dl (P0); 96,20 mg/dl (P1); dan 78,76 mg/dl (P2). Rataan yang terbaik pada pertambahan bobot badan, konsumsi bahan kering harian, dan konversi ransum terdapat pada P2 yaitu 63,96 g/hari, 574,13 g/hari, dan 9,08. Hasil penelitian dapat disimpulkan bahwa mikroenkapsulasi minyak ikan dapat menurunkan kolesterol darah, dengan penurunan tertinggi pada pemberian 5%. (The impact of microencapsulation fish oil in feed on blood cholesterols and performance on sheep) ABSTRAK. This study measured the effect of encapsulated fish oil on blood cholesterol and sheep performance. The study was conducted at the Bunihayu Sheep and Goat Breeding Services Bunihayu, Subang on January 20, 2020 to March 27, 2020. A total of 18 male thin-tailed sheep 15.99±0.98 kg were allocated randomly into 3 treatments. The sheep were given feed supplemented with fish oil microencapsulation of 0% (P0), 2.5% (P1), and 5% (P2). The data were collected and analyzed by analysis of variance and, if the result is significantly different, continued by Duncan's test. The results showed that fish oil microencapsulation decreased blood cholesterol levels (P0.05). However, it did not affect body weight gain, consumption, and feed conversion (P0.05). Decreased levels of cholesterol occurred in the group of sheep with 2.5% microencapsulation (P1) and 5% microencapsulation (P2). Blood cholesterol levels of each treatment were 100.70 mg/dl (P0); 96.20 mg/dl (P1); and 78.76 mg/dl (P2), respectively. Averagely, the highest body weight gain, dry matter intake and feed conversion were found in P2 as much as 63.96 g/day, 574.13 g/day, and 9.08, respectively. The results can be concluded that microencapsulation of fish oil can reduce blood cholesterol, with the highest decrease at the level of 5%.
Estimation of morbidity profile and outcomes of geriatric indoor patients in medicine wards of tertiary care center of Bundelkhand region - A retrospective study
Authors: Tiwari Jyoti , Rawat Sumit , Jain Amit , Biswas Diwashish 
Published: August 2021

The elderly population is increasing rapidly globally, and presently, India has the second largest number of elderly persons in the country. Estimates of health disorders of the elderly in developing countries are required to predict trends in disease burden and to plan better health care facilities for the elderly population in the society. To study the profile of medical disorders & outcomes in the elderly patients admitted in the medicine wards of Bundelkhand Govt. Medical College, Sagar, MP. Which is a rural Government medical college of central India. This is a retrospective, observational study design. The study conducted in the indoor patients of Bundelkhand Medical College & Hospital Sagar, MP in the span of 6 months starting from Feb 2019 to July 2019 & total of 970 patients, aged 60- 90yrs were enrolled. The data were obtained from MRD of BMC Sagar & by review of records, data were collected and statistically analysed. Our study has total (n=970), out of which (n=581, 59.9%) were males & (n=389, 41.1%) were females. Mean age of males- 67.6±7.53, Mean age of females-68.4±7.98. Highest patients were in the age group of 60-69yrs (n=590, 60.8%). Among system involvement, Respiratory system (27%), Cardiovascular system (22.3%), GIT (11.4%), Cerebrovascular (7.7%), Genitourinary (5.7%) , Endocrine (5.1%), Infections (4.7%) and cancers (4.1) .In our patients 75.1% were discharged, 7.2% cases of DOR , 6.2% patients were LAMA. Death was in 4.6% and 0.6% cases were referred to higher center. The study shows highest cases of COPD (15.2%) followed by CAD (13.1%), Pulmonary TB (7.6%), Cerebrovascular accidents (6.1%), Hypertension (6.0%), Diabetes mellitus (4.5%), UTI (4.1%) and cancers (4.1%) in the geriatric patients of our study.
Randomized trial for fungal corneal ulcer- A comparison of outcome between two regimes of medical treatment with topical natamycin and topical voriconazole in a tertiary care Centre
Authors: Sarkar Piyali , Chandra Sarkar Kumaresh , Ranjan Naskar Tridib , Bhattacharyya Shashwat , Chandra Biswas Mukul 
Published: August 2021

Inflammation of the cornea is known as keratitis. Microbial keratitis is a great challenge for the physicians due to its varied presentation, overlapping symptoms and rapid progression. Though bacterial keratitis is the most prevalent in developing countries but recent increasing trend of fungal keratitis carries a significant risk factors and one of the leading causes of vision loss. Early diagnosis and treatment are the cornerstone for its effective control. Purpose: To determine the outcome and efficacy of treatment with topical natamycin and topical voriconazole in different groups. It was a randomised, prospective, comparative, experimental study. The study populations were selected according to inclusion and exclusion criteria after proper evaluation. The study populations were divided into Group A (treated with 1% topical natamycin) and group B (treated 5% topical voriconazole. The patients were followed up subsequently. Data were collected, tabulated in Excel sheet and analyzed in percentage, proportion, t-test and chi square (χ2) test. The statistically significant was considered if p value &#60;0.05. The average age of the study populations was 39.32 ± 14.99 years. Topical voriconazole was found better against primary fungal ulcer than natamycin but not statistically significant (χ2=0.283, p=0.59). The mean healing times of group A and group B were 25.42 ± 4.59 and 24.92 ± 3.99 days respectively. This study concluded that it had male predominance, commonly involved younger people and poor socioeconomic agricultural workers. Both drugs were found effective against primary ulcer but voriconazole was slightly better.
PERFORMANCE ANALYSIS OF UNSIGNALIZED INTERSECTION ON PERJUANGAN AND VETERAN STREET MARTAPURA BANJAR DISTRICT
Authors: Fajar Achmad , Yasruddin Yasruddin 
Published: August 2021

The intersection of Jl. Perjuangan – Jl. Veteran is located in Martapura City, Banjar Regency, South Kalimantan Province. At this intersection there are only cautionary street lights or yellow lights, then the Intersection condition which is the road to residential areas, schools, shops, and traditional markets to support the occurrence of traffic jams and accidents Primary data or data taken from the field include geometric conditions, environmental conditions, side barriers, traffic volume at the Intersection of Jalan Perjuangan - Jalan Veteran Martapura City. Secondary data includes the number of residents in Martapura City and data on the growth of the number of vehicles. Furthermore, the data samples were analyzed using the Indonesian Road Capacity Manual (MKJI, 1997) to find out whether Intersection performance is still feasible or not. If the results of the analysis show that the Intersection performance is no longer feasible, it is necessary to solve the problem. At the intersection, Jl. Perjuangan - Jl. Veteran, Martapura City, Banjar Regency, on a unsignal condition, obtained a degree of saturation (DS) of 0.76 and delay (D) of all intersections of 12.7 seconds / smp with the Service Level Index at B, which indicates that at the intersection still has good conditions. After forecasting analysis, it is found that in the 6th year the degree of saturation (DS) is 1.11 and the whole delay is 26.21 seconds / smp with the Service Level Index in class D where the intersection has reached a bad condition or must be done intersection management analysis. By analyzing the form of intersection management when applied with a signalized intersection, the alternative 2 phase proposal is the best which is seen from the degree of saturation and delay with the value of Degree Saturation (DS) 0.74 and Delay (D) 18,33 seconds / smp with the intersection service level becomes C.
THE DESIGN OF THE CONSTRUCTION OF RETAINING WALLS ON THE RIVER SLOPES OF KUIN
Authors: Yasrifullah Achmad , Adriani Adriani 
Published: August 2021

North Kuin Street, North Kuin, North Banjarmasin Subdistrict, South Kalimantan Sub-district is right on the outskirts of Kuin River. Precisely the road that is in front of the Sultan Suriansyah Mosque, where the road has experienced cracks that can potentially occur landslides. In the event of an avalanche, it will result in obstructed traffic activities on the road which also affect the economy of the surrounding community. So from that the soil retaining wall is needed to maintain the stability of the land on the outskirts of the Kuin River so that landslides do not occur.This design begins with identifying problems that occur. Next is data collection of investigations in the field and laboratory. Then the data obtained are analyzed and interpreted and then visualized in the form of stratigraphy by plotting the type of soil by the results of sondir and boring that have been interpreted. After that, check the initial condition of the slope so that the shape of the avalanche can be identified. Then proceed with calculating the forces acting on the retaining wall due to traffic loads and other loads above it to obtain carrying capacity from the ground. Then proceed with modeling and analysis using Geo Studio 2012 software to see the value of SF (safety factor). At the end of the calculation the volume and price of the work unit are calculated to obtain the amount of the budget plan (RAB). From the results of the analysis of the design of anchor plaster, it was obtained a box profile of FSP VIL steel plaster with a total length of 28 m plaster. At stake uses a steel pipe with a diameter of 91.44 cm which is set at a depth of 28 m. For slope stability with pile reinforcement obtained SF = 1.835> 1.5, it can be said to be safe. Based on the calculation of the volume and price of the work unit, this design requires a cost of Rp. 7,340,166,486, -