Microbial urea-nitrogen recycling in arctic ground squirrels: the effect of ambient temperature of hibernation.

Energy conservation associated with hibernation is maximized at the intersection of low body temperature (T), long torpor bouts, and few interbout arousals. In the arctic ground squirrel (Urocitellus parryii), energy conservation during hibernation is best achieved at ambient temperatures (T) around 0 °C; however, they spend the majority of hibernation at considerably lower T. Because arctic ground squirrels switch to mixed fuel metabolism, including protein catabolism, at extreme low T of hibernation, we sought to investigate how microbial urea-nitrogen recycling is used under different thermal conditions.

Ethical, legal and social aspects of human cerebral organoids and their governance in Germany, the United Kingdom and the United States.

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use.

Multiple copy number variation in a patient with Kleefstra syndrome.

Objective: To report a rare case of a patient with a molecular diagnosis of Kleefstra syndrome (KS) who has four other chromosomal alterations involving pathogenic variants.

Case Description: Male patient, two years old, with global delay, including in neuropsychomotor development, ocular hypertelorism, broad forehead, brachycephaly, hypotonia, ligament laxity, unilateral single palmar crease and arachnoid cyst. The microarray-based comparative genomic hybridization (a-CGH) identified copy number variations (CNVs) in five regions: 9q34.

Characterization of Low-Loss Dielectric Materials for High-Speed and High-Frequency Applications.

In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed on the sample preparation, data collection, and the comparison with the data sheet values provided from vendors. A coplanar waveguide with ground (CPWG) test vehicle with one of these raw dielectric materials (vendor 1) is designed (through Polar and simulation) and fabricated.

Ethical considerations of preconception and prenatal gene modification in the embryo and fetus.

The National Academies of Sciences and Medicine 2020 consensus statement advocates the reinstatement of research in preconception heritable human genome editing (HHGE), despite the ethical concerns that have been voiced about interventions in the germline, and outlines criteria for its eventual clinical application to address monogenic disorders. However, the statement does not give adequate consideration to alternative technologies. Importantly, it omits comparison to fetal gene therapy (FGT), which involves gene modification applied prenatally to the developing fetus and which is better researched and less ethically contentious.

Stable isotope analysis of CO in breath indicates metabolic fuel shifts in torpid arctic ground squirrels.

Stable carbon isotope ratios (δC) in breath show promise as an indicator of immediate metabolic fuel utilization in animals because tissue lipids have a lower δC value than carbohydrates and proteins. Metabolic fuel consumption is often estimated using the respiratory exchange ratio (RER), which has lipid and carbohydrate boundaries, but does not differentiate between protein and mixed fuel catabolism at intermediate values. Because lipids have relatively low δC values, measurements of stable carbon isotopes in breath may help distinguish between catabolism of protein and mixed fuel that includes lipid.

Inhibition of interleukin-5 induced false positive anti-drug antibody responses against mepolizumab through the use of a competitive blocking antibody.

Mepolizumab, a humanized IgG1 monoclonal antibody that blocks native homodimeric interleukin-5 (IL-5) from binding to the IL-5 receptor, has recently been approved for treatment of severe eosinophilic asthma. Our initial immunogenicity assay method for phase I and II studies utilized a bridging electrochemiluminescence format with biotin and ruthenium-labelled mepolizumab linked by anti-drug antibodies (ADA). We discovered that IL-5 significantly increased in dosed subjects from a phase II study and that the increased IL-5 was in the form of a drug-bound complex.

Development of an ultra-sensitive single molecule counting assay for the detection of interleukin-13 as a marker for asthmatic severity.

Objective: Interleukin-13 (IL-13) has been difficult to quantify within human serum due to low abundance. Available assays have not been sensitive enough to detect IL-13 at the femtogram level. Thus, there are inconsistencies within the published literature as to IL-13 concentrations in normal or disease populations.

Thermogenic capacity at subzero temperatures: how low can a hibernator go?

Abstract Hibernation in mammals is a physiological and behavioral adaptation to survive intervals of low resource availability through profound decreases in metabolic rate (MR), core body temperature (Tb), and activity. Most small mammalian hibernators thermoconform, with Tb approximating ambient temperature (Ta); arctic species are an exception, since they must actively defend what can be large thermal gradients between Tb and Ta. Here we compare the thermogenic capacity of the arctic ground squirrel (Urocitellus parryii) to that of the golden-mantled ground squirrel (Callospermophilus lateralis), a temperate-zone montane hibernator.

The principle of symmetry in acupuncture and its clinical applications.

The clinical practice of acupuncture and study of the traditional Chinese medicine literature has led to the observation that if the diaphragm is used as an axis of symmetry, there are many symmetrical points on the upper and lower halves of the body. The symmetrical points share several common properties, including physiological functions, mechanisms of pathogenesis and therapeutic effects. Employing these corresponding points on the upper and lower parts of the body simultaneously can frequently enhance the therapeutic outcome rather substantially.

Assessment of the 9-item Patient Health Questionnaire (PHQ-9) as a screen tool for symptoms of depression in community caregivers for adults with intellectual disabilities.

The study aim was to determine the extent and determinants of reporting depressive symptoms in caregivers for persons with intellectual disabilities based on assessment of the 9-item Patient Health Questionnaire (PHQ-9). A cross-sectional study was conducted, recruiting 455 caregivers for adults with ID who were providing care in community residences, with complete PHQ-9 data being analyzed. The results indicated that the mean of each item scored on the PHQ-9 varied from 0.

False-positive immunogenicity responses are caused by CD20+ B cell membrane fragments in an anti-ofatumumab antibody bridging assay.

An electrochemiluminescent (ECL) bridging assay to detect anti-ofatumumab antibodies (ADA) in human serum samples was developed and validated. Using this assay format, clinical samples were first screened to identify potential ADA positive samples, which were then further tested by adding excess drug, confirming the positive signals as drug specific. However, when the method was implemented into clinical studies for ADA testing, a high positive rate was observed in the pre-dose samples collected from patients with chronic lymphocytic leukemia (CLL).

Development of an enzymatic assay for the detection of neutralizing antibodies against therapeutic angiotensin-converting enzyme 2 (ACE2).

Therapeutic proteins have the potential to elicit immune responses in animals and humans (Mire-Sluis et al., 2004; Yu et al., 2006; Shankar et al.

A test of alternative models for increased tissue nitrogen isotope ratios during fasting in hibernating arctic ground squirrels.

We describe two models explaining the increase in tissue nitrogen isotope ratios (δ(15)N) that occurs during fasting in animals. The catabolic model posits that protein breakdown selectively removes the lighter isotope of nitrogen ((14)N) from catabolized tissues, causing an increase in the proportion of heavy nitrogen isotope ((15)N). The anabolic model posits that protein synthesis during fasting results in elevated δ(15)N values, as the unreplaced loss of (14)N to urea results in a higher proportion of (15)N in plasma amino acids used for protein synthesis.

Estimating lean mass over a wide range of body composition: a calibration of deuterium dilution in the arctic ground squirrel.

Calculating body water through isotope dilution has become a useful way to nondestructively estimate body composition in many species. The most accurate estimates using this method require calibration against proximate chemical analysis of body composition for individual species, but no studies to our knowledge have calibrated this method on a hibernating mammal that seasonally undergoes dramatic changes in body composition. We use deuterium oxide to estimate total body water in captive arctic ground squirrels, Urocitellus parryii, and compare two approaches of calculating lean mass from total body water, both calibrated against lean mass based on proximate analysis.

Development and validation of a cell-based SEAP reporter assay for the detection of neutralizing antibodies against an anti-IL-13 therapeutic antibody.

A cell-based bioassay capable of detecting neutralizing antibodies (NAb) specific to a therapeutic anti-IL-13 monoclonal antibody was developed, validated and used to analyze normal human and asthma serum samples. At the time of this study, a neutralizing assay was unavailable for anti-IL-13 antibody therapeutics with sufficient rigor for validation. Thus, we describe here a method and considerations for validation.

Hibernating above the permafrost: effects of ambient temperature and season on expression of metabolic genes in liver and brown adipose tissue of arctic ground squirrels.

Hibernating arctic ground squirrels (Urocitellus parryii), overwintering in frozen soils, maintain large gradients between ambient temperature (T(a)) and body temperature (T(b)) by substantially increasing metabolic rate during torpor while maintaining a subzero T(b). We used quantitative reverse-transcription PCR (qRT-PCR) to determine how the expression of 56 metabolic genes was affected by season (active in summer vs hibernating), metabolic load during torpor (imposed by differences in T(a): +2 vs -10°C) and hibernation state (torpid vs after arousal). Compared with active ground squirrels sampled in summer, liver from hibernators showed increased expression of genes associated with fatty acid catabolism (CPT1A, FABP1 and ACAT1), ketogenesis (HMGCS2) and gluconeogenesis (PCK1) and decreased expression of genes associated with fatty acid synthesis (ACACB, SCD and ELOVL6), amino acid metabolism, the urea cycle (PAH, BCKDHA and OTC), glycolysis (PDK1 and PFKM) and lipid metabolism (ACAT2).

Physical and mental health status of staff working for people with intellectual disabilities in Taiwan: measurement with the 36-Item Short-Form (SF-36) health survey.

Little explicit attention has been given to the generic health profile of staff working for people with intellectual disability in institutions. This study aimed to provide a profile of physical and mental health of staff working in disability welfare institutions, and to examine the possible demographic and organizational factors that explain an association with their health. A cross-sectional questionnaire survey was conducted to analyze 1243 staff (76% response rate) working in 24 institutions in Taiwan.

Extrinsic high-effort and low-reward conditions at work among institutional staff caring for people with intellectual disabilities in Taiwan.

The purposes of the present study were to determine whether extrinsic high-effort/low-reward conditions at work are associated with personal characteristics and the organizational environments. A cross-sectional survey was conducted (76.7% response rate, N=1243) by recruiting the staff caring for people with intellectual disabilities of Taiwan in 2006.

Job strain and determinants in staff working in institutions for people with intellectual disabilities in Taiwan: a test of the Job Demand-Control-Support model.

Little is known about the job strain of staff working in disability institutions. This study investigated the staff's job strain profile and its determinants which included the worker characteristics and the psychosocial working environments in Taiwan. A cross-sectional study survey was carried out among 1243 workers by means of a self-answered questionnaire.

Red tides in the Gulf of Mexico: Where, when, and why?

[1] Independent data from the Gulf of Mexico are used to develop and test the hypothesis that the same sequence of physical and ecological events each year allows the toxic dinoflagellate Karenia brevis to become dominant. A phosphorus-rich nutrient supply initiates phytoplankton succession, once deposition events of Saharan iron-rich dust allow Trichodesmium blooms to utilize ubiquitous dissolved nitrogen gas within otherwise nitrogen-poor sea water. They and the co-occurring K.

Alloxan is an inhibitor of O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase.

We have previously shown that streptozotocin (STZ) inhibits O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase (O-GlcNAcase), the enzyme that removes O-GlcNAc from proteins. In light of this observation, we explored the possibility that the diabetogenic toxin alloxan, an O-GlcNAc transferase (OGT) inhibitor, might also inhibit O-GlcNAcase. Alloxan inhibited islet O-GlcNAcase with a dose-response much like that of STZ.