Microalgae Biofuel for a Heavy-Duty Transport Sector within Planetary Boundaries.

In this contribution, we study the extent to which 68 scenarios for microalgae biofuels could help the heavy-duty transport sector operate within planetary boundaries. The proposed scenarios are built considering a range of alternative configurations based on three types of fuel production processes (i.e., transesterification, hydrodeoxygenation, and hydrothermal liquefaction), different carbon sources (such as natural gas power plants and direct air capture), byproduct treatments, and two electricity mixes. Our results reveal that microalgae biofuels could significantly reduce the environmental and human health impacts of the business-as-usual (fossil-based) heavy-duty transport sector. Moreover, relative to standard biofuels that show large land-use requirements, we find that microalgae biofuels also decrease the damage on biosphere integrity substantially. Notably, pathways resorting to hydrodeoxygenation of microalgae oil and direct air capture and carbon storage could reduce the current impact induced globally on climate change by the heavy transport by 77%, while attaining six-fold reductions in biosphere integrity impacts, both relative to conventional biofuels.

Unexpected sound omissions are signaled in human posterior superior temporal gyrus: an intracranial study.

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes.

Intracranial Recordings Demonstrate Both Cortical and Medial Temporal Lobe Engagement in Visual Search in Humans.

Visual search is a fundamental human behavior, providing a gateway to understanding other sensory domains as well as the role of search in higher-order cognition. Search has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In this study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous intracranial work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity, manifesting as activity increase in Pop-out as compared to Search, in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.

Gender bias in academia: A lifetime problem that needs solutions.

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: This study aimed to evaluate the safety of avacopan, an orally administered C5a receptor inhibitor, for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in addition to standard-of-care (SOC) treatment with glucocorticoids with cyclophosphamide or rituximab. METHODS: In this randomized 12-week study, twice daily avacopan (10 mg or 30 mg) plus SOC was assessed versus SOC only in patients with newly diagnosed/relapsing ANCA-associated vasculitis. Efficacy measurements included 50% or greater reduction in Birmingham Vasculitis Activity Score (BVAS) at day 85, rapid reduction (day 29) of BVAS to a score of 0 that was sustained through day 85, change in Vasculitis Damage Index (VDI), renal response (improvement in estimated glomerular filtration rate [eGFR], hematuria, and albuminuria), and health-related quality of life (HRQoL). RESULTS: Forty-two patients were randomized (n = 13 SOC, n = 13 avacopan 10 mg, and n = 16 avacopan 30 mg). Serious adverse events occurred in 15% and 17% of patients receiving SOC only and patients receiving avacopan with SOC, respectively. In the intent-to-treat population, BVAS response was high across arms (11 of 13 SOC, 11 of 12 avacopan 10 mg, and 12 of 15 avacopan 30 mg); increases in mean VDI were greater with SOC only than with avacopan plus SOC (0.3 versus 0.1). Avacopan 30 mg was numerically superior to placebo and avacopan 10 mg in early remission (15%, 8%, and 20% for SOC only, avacopan 10 mg, and avacopan 30 mg, respectively), improved eGFR (+2.0 ml/min/1.73m2 , +1.3 ml/min/1.73m2 , and +6.2 ml/min/1.73m2 , respectively), renal response (17%, 40%, and 63%, respectively), and measures of HRQoL. CONCLUSION: Avacopan in addition to SOC for ANCA-associated vasculitis was well tolerated, and at the higher study dose, it appeared to improve time to remission (ClinicalTrials.gov identifier NCT02222155).

Maternal SIN3A regulates reprogramming of gene expression during mouse preimplantation development.

The oocyte-to-embryo transition entails genome activation and a dramatic reprogramming of gene expression that is required for continued development. Superimposed on genome activation and reprogramming is development of a transcriptionally repressive state at the level of chromatin structure. Inducing global histone hyperacetylation relieves this repression and histone deacetylases 1 and 2 (HDAC1 and HDAC2) are involved in establishing the repressive state. Because SIN3A is an HDAC1/2-containing complex, we investigated whether it is involved in reprogramming gene expression during the course of genome activation. We find that Sin3a mRNA is recruited during maturation and that inhibiting its recruitment not only inhibits development beyond the 2-cell stage but also compromises the fidelity of reprogramming gene expression. The SIN3A that is synthesized during oocyte maturation reaches a maximum level in the mid-1-cell embryo and is essentially absent by the mid-2-cell stage. Overexpressing SIN3A in 1-cell embryos has no obvious effect on pre- and postimplantation development. These results provide a mechanism by which reprogramming can occur using a maternally inherited transcription machinery, namely, recruitment of mRNAs encoding transcription factors and chromatin remodelers, such as SIN3A.

The emerging HIV epidemic on the Mexico-U.S. border: an international case study characterizing the role of epidemiology in surveillance and response.

PURPOSE: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome surveillance data are critical for monitoring epidemic trends, but they can mask dynamic subepidemics, especially in vulnerable populations that underuse HIV testing. In this case study, we describe community-based epidemiologic data among injection drug users (IDUs) and female sex workers (FSWs) in two northern Mexico-U.S. border states that identified an emerging HIV epidemic and generated a policy response. METHODS: We draw from quantitative and qualitative cross-sectional and prospective epidemiologic studies and behavioral intervention studies among IDUs and FSWs in Tijuana, Baja California, and Ciudad Juarez, Chihuahua. RESULTS: The recognition that the HIV epidemic on Mexico's northern border was already well established in subgroups in whom it had been presumed to be insignificant was met with calls for action and enhanced prevention efforts from researchers, nongovernmental organizations, and policy makers. CONCLUSIONS: Successful policies and program outcomes included expansion of needle-exchange programs, a nationwide mobile HIV prevention program targeting marginalized populations, a successful funding bid from the Global Fund for HIV, TB, and Malaria to scale up targeted HIV-prevention programs, and the establishment of bi-national training programs on prevention of HIV and substance use. We discuss how epidemiologic data informed HIV prevention policies and suggest how other countries may learn from Mexico's experience.

Detection of low levels of the mitochondrial tRNALeu(UUR) 3243A>G mutation in blood derived from patients with diabetes.

BACKGROUND: Mutations in the human mitochondrial genome have been suspected to play a significant role in the etiological development of mitochondrial diabetes. Detection of the 3243A>G mutation in the mitochondrial transfer RNALeu(UUR) gene (MTTL1), especially at low heteroplasmy levels, is highly desirable since it facilitates the diagnosis and subsequent management of the disease. The proportions of mutant mitochondrial DNA (mtDNA) can vary between tissues and are usually significantly higher in muscle than in blood, but muscle biopsies from patients with diabetes are rarely available. METHODS: Here, we describe a technique that can not only determine the presence of MTTL1 3243A>G, but can also estimate the percentage of mutant DNA. The technique is based on the use of the WAVE system for the high-performance liquid chromatography (HPLC)-mediated analysis of mutation-specific restriction fragments derived from mutant PCR amplicons. PCR amplicon restriction fragment analysis by HPLC (PARFAH) can also be used for the detection of other mutations. RESULTS: This PARFAH analytical approach led to the discovery of the 3243A>G mutation in blood samples from a series of patients who had initially been reported to lack the mutation, even though matrilineal relatives had been shown to harbor the mutation associated with maternally inherited diabetes and deafness (MIDD) or mitochondrial myopathy encephalopathy lactic acidosis stroke-like episodes (MELAS) phenotypes. We have established that the PARFAH method can reliably detect as little as 1% mutant DNA in a sample, which would normally be missed by commonly used gel electrophoresis or sequencing methods. CONCLUSIONS: The PARFAH method not only provides a sensitive, high-throughput, and cost-effective strategy for the detection of low levels of mtDNA mutations in peripheral tissues, but also facilitates the estimation of the percentage of mutant DNA in the sample. The fact that samples can be readily obtained from peripheral tissues in many cases will avoid the need for invasive muscle biopsies. Our ability to detect low levels of mtDNA mutations in blood samples of carriers will allow us to reassess the prevalence of the MTTL1 3243A>G mutation in patients with diabetes.

A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia.

Actin, one of the major filamentous cytoskeletal molecules, is involved in a variety of cellular functions. Whereas an association between muscle actin mutations and skeletal and cardiac myopathies has been well documented, reports of human disease arising from mutations of nonmuscle actin genes have been rare. We have identified a missense point mutation in the gene coding for beta -actin that results in an arginine-to-tryptophan substitution at position 183. The disease phenotype includes developmental midline malformations, sensory hearing loss, and a delayed-onset generalized dystonia syndrome in monozygotic twins. Cellular studies of a lymphoblastoid cell line obtained from an affected patient demonstrated morphological abnormalities of the actin cytoskeleton and altered actin depolymerization dynamics in response to latrunculin A, an actin monomer-sequestering drug. Resistance to latrunculin A was also observed in NIH 3T3 cells expressing the mutant actin. These findings suggest that mutations in nonmuscle actins may be associated with a broad spectrum of developmental malformations and/or neurological abnormalities such as dystonia.

BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex.

Motor training can induce profound physiological plasticity within primary motor cortex, including changes in corticospinal output and motor map topography. Using transcranial magnetic stimulation, we show that training-dependent increases in the amplitude of motor-evoked potentials and motor map reorganization are reduced in healthy subjects with a val66met polymorphism in the brain-derived neurotrophic factor gene (BDNF), as compared to subjects without the polymorphism. The results suggest that BDNF is involved in mediating experience-dependent plasticity of human motor cortex.

HIV/AIDS practice patterns, knowledge, and educational needs among Hispanic clinicians in Texas, USA, and Nuevo Leon, Mexico / Prácticas, conocimientos y necesidades educativas sobre VIH/sida de los médicos hispanos en Texas, Estados Unidos, y Nuevo León, México

Hispanic clinicians in Texas, United States of America, and in the neighboring state of Nuevo Leon, Mexico, were surveyed to determine their educational needs in the area of HIV/AIDS. Two-thirds of the 74 Texan and 22% of the 104 Mexican physicians queried had seen at least one HIV/AIDS patient in the previous year. The majority of the respondents were primary care physicians who: 1) were in private practice; 2) saw more than 1 000 patients per year; 3) had been out of training for more than 10 years; 4) provided some HIV prevention education to patients based on their perceived risk of infection; 5) rated their own knowledge of HIV/AIDS as average but rated their knowledge of treatments for the disease below average; 6) received most of their information about HIV/AIDS from journals rather than formal continuing education programs; 7) thought Hispanic patients had special needs with regard to HIV/AIDS care; and 8) were willing to attend education programs to improve their HIV/AIDS management skills. The greatest barriers to caring for HIV patients were lack of clinical knowledge and fear of infection. These results point to a need for a large-scale training program to improve the HIV/AIDS management skills of Hispanic clinicians in Texas and Nuevo Leon.

Los médicos hispanos que ejercen en Texas, Estados Unidos de América, y en el estado vecino de Nuevo León, México, fueron encuestados para determinar si necesitaban recibir capacitación en materia de VIH/sida. Dos terceras partes de los 74 médicos interrogados en Texas y 22% de los 104 interrogados en Nuevo León habían examinado como mínimo a un paciente de VIH/sida durante el año previo. La mayoría de los encuestados eran médicos de atención primaria que 1) ejercían su profesión en lo privado; 2) veían a más de 1000 pacientes al año; 3) habían terminado sus estudios hacía más de 10 años; 4) proporcionaban educación preventiva a sus pacientes según la impresión que tuvieran del riesgo de cada uno; 5) dijeron poseer conocimientos normales sobre VIH/sida, pero inferiores a lo normal en lo referente a su tratamiento; 6) sacaban la mayor parte de su información sobre VIH/sida de revistas, y no de programas de educación continuada; 7) opinaban que los pacientes hispanos tenían necesidades especiales en torno a VIH/sida, y 8) estaban dispuestos a asistir a programas educativos para mejorar su habilidad en el manejo de pacientes con VIH/sida. Los factores que más obstaculizaban la atención de los pacientes con infección por VIH fueron la falta de conocimientos sobre los aspectos clínicos de la enfermedad y el temor a infectarse. Estos resultados apuntan hacia la necesidad de establecer un programa de adiestramiento a gran escala para mejorar la habilidad de los médicos hispanos en Texas y Nuevo León para tratar a pacientes con VIH/sida.