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Ventral midbrain dopaminergic neurons project to the striatum as well as the cortex and are involved in movement control and reward-related cognition. In Parkinson’s disease, nigrostriatal midbrain dopaminergic neurons degenerate and cause typical Parkinson’s disease motor-related impairments, while the dysfunction of mesocorticolimbic midbrain dopaminergic neurons is implicated in addiction and neuropsychiatric disorders. Study of the development and selective neurodegeneration of the human dopaminergic system, however, has been limited due to the lack of an appropriate model and access to human material. Here, we have developed a human in vitro model that recapitulates key aspects of dopaminergic innervation of the striatum and cortex. These spatially arranged ventral midbrain–striatum–cortical organoids (MISCOs) can be used to study dopaminergic neuron maturation, innervation and function with implications for cell therapy and addiction research. We detail protocols for growing ventral midbrain, striatal and cortical organoids and describe how they fuse in a linear manner when placed in custom embedding molds. We report the formation of functional long-range dopaminergic connections to striatal and cortical tissues in MISCOs, and show that injected, ventral midbrain-patterned progenitors can mature and innervate the tissue. Using these assembloids, we examine dopaminergic circuit perturbations and show that chronic cocaine treatment causes long-lasting morphological, functional and transcriptional changes that persist upon drug withdrawal. Thus, our method opens new avenues to investigate human dopaminergic cell transplantation and circuitry reconstruction as well as the effect of drugs on the human dopaminergic system.

Neptune-sized planets exhibit a wide range of compositions and densities, depending on factors related to their formation and evolution history, such as the distance from their host stars and atmospheric escape processes. They can vary from relatively low-density planets with thick hydrogen–helium atmospheres1,2to higher-density planets with a substantial amount of water or a rocky interior with a thinner atmosphere, such as HD 95338 b (ref. 3), TOI-849 b (ref. 4) and TOI-2196 b (ref. 5). The discovery of exoplanets in the hot-Neptune desert6, a region close to the host stars with a deficit of Neptune-sized planets, provides insights into the formation and evolution of planetary systems, including the existence of this region itself. Here we show observations of the transiting planet TOI-1853 b, which has a radius of 3.46 ± 0.08 Earth radii and orbits a dwarf star every 1.24 days. This planet has a mass of 73.2 ± 2.7 Earth masses, almost twice that of any other Neptune-sized planet known so far, and a density of 9.7 ± 0.8 grams per cubic centimetre. These values place TOI-1853 b in the middle of the Neptunian desert and imply that heavy elements dominate its mass. The properties of TOI-1853 b present a puzzle for conventional theories of planetary formation and evolution, and could be the result of several proto-planet collisions or the final state of an initially high-eccentricity planet that migrated closer to its parent star.

Two-dimensional neuronal cultures have a limited ability to recapitulate the in vivoenvironment of the brain. Here, we introduce a three-dimensional in vitromodel for human glia-to-neuron conversion, surpassing the spatial and temporal constrains of two-dimensional cultures. Focused on direct conversion to induced dopamine neurons (iDANs) relevant to Parkinson disease, the model generates functionally mature iDANs in 2 weeks and allows long-term survival. As proof of concept, we use single-nucleus RNA sequencing and molecular lineage tracing during iDAN generation and find that all glial subtypes generate neurons and that conversion relies on the coordinated expression of three neural conversion factors. We also show the formation of mature and functional iDANs over time. The model facilitates molecular investigations of the conversion process to enhance understanding of conversion outcomes and offers a system for in vitroreprogramming studies aimed at advancing alternative therapeutic strategies in the diseased brain.

This study presents the diversity of mosquitoes collected from communes, endemic with malaria and dengue, located in Khanh Hoa and Binh Phuoc Provinces, Vietnam. A total of 10,288 mosquitoes were collected in the village and forested sites using standard larval dippers, cow-baited traps, ultra-violet light traps, and mechanical aspirators. Mosquito taxa were identified morphologically and species complexes/groups were further characterized molecularly. Five genera of mosquitoes were morphologically identified: Anopheles Meigen(21 species), Aedes Meigen(2 species), Culex Linnaeus(5 species), Mansonia Blanchardsp., and Armigeres Theobaldsp. The PCR-based identification methods allowed the distinction of members of Maculatus Group, Funestus Group, and Dirus Complex; and DNA barcodes enabled the further identification of the Barbirostris Complex. Data reported here include the first report of An. saeungaeTaai & Harbach and An. wejchoochoteiTaai & Harbach from Vietnam, and re-emphasizes the significance of using molecular data in an integrated systematic approach to identify cryptic species and better understand their role in disease transmission.

Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitroor transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

The atmospheres of gaseous giant exoplanets orbiting close to their parent stars (hot Jupiters) have been probed for nearly two decades1,2. They allow us to investigate the chemical and physical properties of planetary atmospheres under extreme irradiation conditions3. Previous observations of hot Jupiters as they transit in front of their host stars have revealed the frequent presence of water vapour4and carbon monoxide5in their atmospheres; this has been studied in terms of scaled solar composition6under the usual assumption of chemical equilibrium. Both molecules as well as hydrogen cyanide were found in the atmosphere of HD 209458b5,7,8, a well studied hot Jupiter (with equilibrium temperature around 1,500 kelvin), whereas ammonia was tentatively detected there9and subsequently refuted10. Here we report observations of HD 209458b that indicate the presence of water (H2O), carbon monoxide (CO), hydrogen cyanide (HCN), methane (CH4), ammonia (NH3) and acetylene (C2H2), with statistical significance of 5.3 to 9.9 standard deviations per molecule. Atmospheric models in radiative and chemical equilibrium that account for the detected species indicate a carbon-rich chemistry with a carbon-to-oxygen ratio close to or greater than 1, higher than the solar value (0.55). According to existing models relating the atmospheric chemistry to planet formation and migration scenarios3,11,12, this would suggest that HD 209458b formed far from its present location and subsequently migrated inwards11,13. Other hot Jupiters may also show a richer chemistry than has been previously found, which would bring into question the frequently made assumption that they have solar-like and oxygen-rich compositions.

In patients who have experienced near-drowning, hypoxemia is the major clinical consequence. We report two cases of patients who have experienced near-drowning in freshwater who were successfully treated with nasal-continuous [...]

Ticks and tick-borne diseases represent major threats to the public health of the Mongolian population, of which an estimated 26% live a traditional nomadic pastoralist lifestyle that puts them at increased risk for exposure. Ticks were collected by dragging and removal from livestock in Khentii, Selenge, Tuv, and Umnugovi aimags (provinces) during March-May 2020. Using next-generation sequencing (NGS) with confirmatory PCR and DNA sequencing, we sought to characterize the microbial species present in Dermacentor nuttalli(n = 98), Hyalomma asiaticum(n = 38), and Ixodes persulcatus(n = 72) tick pools. Rickettsiaspp. were detected in 90.4% of tick pools, with Khentii, Selenge, and Tuv tick pools all having 100% pool positivity. Coxiellaspp. were detected at an overall pool positivity rate of 60%, while Francisellaspp. were detected in 20% of pools and Borreliaspp. detected in 13% of pools. Additional confirmatory testing for Rickettsia-positive pools demonstrated Rickettsia raoultii(n = 105), CandidatusRickettsia tarasevichiae (n = 65) and R. slovaca/R. sibirica(n = 2), as well as the first report of CandidatusRickettsia jingxinensis (n = 1) in Mongolia. For Coxiellaspp. reads, most samples were identified as a Coxiellaendosymbiont (n = 117), although Coxiella burnetiiwas detected in eight pools collected in Umnugovi. Borreliaspecies that were identified include Borrelia burgdorferisensu lato (n = 3), B. garinii(n = 2), B. miyamotoi(n = 16), and B. afzelii(n = 3). All Francisellaspp. reads were identified as Francisellaendosymbiont species. Our findings emphasize the utility of NGS to provide baseline data across multiple tick-borne pathogen groups, which in turn can be used to inform health policy, determine regions for expanded surveillance, and guide risk mitigation strategies.

Aims. We present data to improve the known parameters of the HD 17156 system (peculiar due to the eccentricity and long orbital period of its transiting planet) and constrain the presence of stellar companions.

We present iron abundance analysis for 23 wide binaries with main sequence components in the temperture range 4900–6300 K, taken from the sample of the pairs currently included in the radial velocity planet search on going at the Telescopio Nazionale Galileo (TNG) using the high resolution spectrograph SARG. The use of a line-by-line differential analysis technique between the components of each pair allows us to reach errors of about 0.02 dex in the iron content difference. Most of the pairs have abundance differences lower than 0.02 dex and there are no pairs with differences larger than 0.07 dex. The four cases of differences larger than 0.02 dex may be spurious because of the larger error bars affecting pairs with large temperature difference, cold stars and rotating stars. The pair HD 219542, previously reported by us to have a different composition, here is shown to be normal. For non-rotating stars warmer than 5500 K, characterized by a thinner convective envelope and for which our analyis appears to be of higher accuracy, we are able to exclude in most cases the consumption of more than 1 Earth Mass of iron (about 5 Earth masses of meteoritic material) during the main sequence lifetime of the stars, placing more stringent limits (about 0.4 Earth masses of iron) in five cases of warm stars. This latter limit is similar to the estimates of rocky material accreted by the Sun during its main sequence lifetime. Combining the results of the present analysis with those for the Hyades and Pleiades, we conclude that the hypothesis that pollution by planetary material is the only mechanism responsible for the highest metallicity of the stars with planets may be rejected at more than 99% level of confidence if the incidence of planets in these samples is as high as 8% and similar to the field stars included in current radial velocity surveys. However, the significance of this result drops considerably if the incidence of planets around stars in binary systems and clusters is less than a half of that around normal field stars.

The star HD 219542 B has been reported by us (Desidera et al. 2003) to show low-amplitude radial velocity variations that could be due to the presence of a Saturn-mass planetary companion or to stellar activity phenomena. In this letter we present the results of the continuation of the radial velocity monitoring as well as a discussion of literature determinations of the chromospheric activity of the star (Wright et al. 2004). These new data indicate that the observed radial velocity variations are likely related to stellar activity. In particular, there are indications that HD 219542 B underwent a phase of enhanced stellar activity in 2002 while the activity level has been lower in both 2001 and 2003. Our 2003 radial velocity measurements now deviate from our preliminary orbital solution and the peak in the power spectrum at the proposed planet period is severely reduced by the inclusion of the new data. We therefore dismiss the planet hypothesis as the cause of the radial velocity variations.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the oral or pharyngeal region. Prospective studies have established the adverse cardiovascular consequences of OSA, including an increased risk for developing hypertension, coronary artery disease, stroke, and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA include intermittent hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the renin-angiotensin-aldosterone system and endothelial dysfunction. OSA should be suspected in hypertensive individuals, particularly in patients with resistant hypertension. CPAP treatment reduces blood pressure, and its effects are more pronounced in patients with high baseline blood pressure and elevated treatment compliance. At present, no clear evidence supports CPAP treatment for primary or secondary cardiovascular disease prevention.

Identificar preditores clínicos, laboratoriais e radiológicos da infecção por Bordetella pertussis.

The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.

This study describes the case of a health professional infected first by influenza virus A(H3N2) and then by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 11 days later. Respiratory samples and clinical data were collected from the patient and from close contacts. RNA was extracted from samples and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the viruses. The patient presented with two different illness events: the first was characterized by fever, chest and body pain, prostration and tiredness, which ceased on the ninth day; RT-qPCR was positive only for influenza virus A(H3N2). Eleven days after onset of the first symptoms, the patient presented with sore throat, nasal congestion, coryza, nasal itching, sneezing and coughing, and a second RT-qPCR test was positive only for SARS-CoV-2; in the second event, symptoms lasted for 11 days. SARS-CoV-2 sequencing identified the Omicron BA.1 lineage. Of the patient's contacts, one was coinfected with influenza A(H3N2) and SARS-CoV-2 lineage BA.1.15 and the other two were infected only with SARS-CoV-2, one also with Omicron BA.1.15 and the other with BA.1.1. Our findings reinforce the importance of testing for different viruses in cases of suspected respiratory viral infection during routine epidemiological surveillance because common clinical manifestations of COVID-19 mimic those of other viruses, such as influenza. [ABSTRACT FROM AUTHOR]

The livestock industry in Mongolia accounts for 24% of national revenue, with one third of the population maintaining a pastoral lifestyle. This close connection between Mongolian population and livestock is a major concern for pathogen transfer, especially given the increase in vector-borne diseases globally. This study examines blood samples from livestock to assess the prevalence of tick-borne bacterial infections across three provinces in Mongolia (Dornogovi, Selenge, Töv). Whole blood samples from 243 livestock (cattle=38, camel=11, goat=85, horse=22, sheep=87) were analyzed with 16S metagenomics next-generation sequencing (NGS) to screen for bacterial pathogens. Positive-NGS samples for Anaplasma, Bartonella, Ehrlichia, Francisella, Leptospira, and Rickettsiawere confirmed by conventional PCR and DNA sequencing. Prevalence rates of Anaplasma, Bartonella, and Ehrlichiawere 57.6%, 12.8%, and 0.4%, respectively. A significant difference in the prevalence of Anaplasmaspp. in livestock by province was observed, with a higher prevalence in Selenge (74.2%, p<0.001) and Töv (64.2% p=0.006) compared to the semi-arid region of Dornogovi (39.8%). In contrast, no association was observed in Bartonellaprevalence by provinces. All Anaplasmasequences (N=139) were characterized as A. ovis. For Bartonellaspecies characterization, phylogenetic analyses of gltA and rpoB genes identified three Bartonellaspecies including B. bovis, B. melophagiand CandidatusB. ovis. Bartonella boviswas detected in all 22-positive cattle, while B. melophagiand CandidatusB. ovis were found in four and three sheep, respectively. This study identifies a high prevalence of tick-borne pathogens within the livestock population and to our knowledge, is the first time NGS methods have been used to explore tick-borne diseases in Mongolia. Further research is needed in Mongolia to better understand the clinical and economic burdens associated with tick-borne diseases in both livestock and pastoral herder populations.

Idiopathic pulmonary fibrosis (IPF) is defined as a chronic fibrosing interstitial disease of unknown cause, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP); it generally progresses into respiratory failure and death. Although progression of the disease is the most common cause of death, there are increasing reports of its association with other pathologies has been reported: e.g., IPF patients seem more susceptible to cardiovascular diseases. Therefore, other pathologies might also influence the natural course.

As part of our radial velocity planet-search survey performed with SARG at TNG, we monitored the components of HD 132563 for ten years. It is a binary system formed by two rather similar solar type stars with a projected separation of 4.1 arcsec, which corresponds to 400 AU at the distance of 96 pc. The two components are moderately metal-poor ([Fe/H] = –0.19), and the age of the system is about 5 Gyr. We detected RV variations of HD 132563B with period of 1544 days and semi-amplitude of 26 m/s. From the star characteristics and line profile measurements, we infer their Keplerian origin. Therefore HD 132563B turns out to host a planet with a projected mass msini= 1.49   MJat 2.6 AU with a moderately eccentric orbit (e= 0.22). The planet around HD 132563B is one of the few that are known in triple stellar systems, as we found that the primary HD 132563A is itself a spectroscopic binary with a period longer than 15 years and an eccentricity higher than 0.65. The spectroscopic component was not detected in adaptive-optics images taken with the instrument AdOpt mounted at the TNG, since it expected at a projected separation that was smaller than 0.2 arcsec at the time of our observations. A small excess in Kband difference between the components with respect to the difference in Vband is compatible with a companion of about 0.55   M⊙. A preliminary statistical analysis of when planets occur in triple systems indicate a similar frequency of planets around the isolated component in a triple system, components of wide binaries and single stars. There is no significant iron abundance difference between the components. The lack of stars in binary systems and open clusters showing strong enhancements of iron abundance, which are comparable to the typical metallicity difference between stars with and without giant planets, agrees with the idea that accretion of planetary material producing iron abundance anomalies over 0.1 dex is rare.