The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.

General Situation:
A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. With the anticyclone aloft strengthening in the middle and latter parts of this week, the weather over southern China will improve and it will be hot.

Date/Month: 10/05 (Sunday)
Wind: South force 3.
Weather: Sunny intervals and a few showers. Isolated thunderstorms later.
Temp range: 28 - 32 C
R.H. range: 65 - 95 per Cent

Date/Month: 11/05 (Monday)
Wind: South force 2 to 3.
Weather: Mainly cloudy with occasional showers and a few squally thunderstorms.
Temp range: 26 - 30 C
R.H. range: 70 - 95 per Cent

Date/Month: 12/05 (Tuesday)
Wind: Light winds force 2.
Weather: Mainly cloudy with a few showers and thunderstorms.
Temp range: 25 - 29 C
R.H. range: 70 - 95 per Cent

Date/Month: 13/05 (Wednesday)
Wind: Southeast force 3.
Weather: Sunny intervals and one or two showers.
Temp range: 26 - 30 C
R.H. range: 65 - 90 per Cent

Date/Month: 14/05 (Thursday)
Wind: Southeast force 3.
Weather: Sunny periods.
Temp range: 26 - 31 C
R.H. range: 60 - 85 per Cent

Date/Month: 15/05 (Friday)
Wind: South to southeast force 3.
Weather: Sunny periods.
Temp range: 27 - 32 C
R.H. range: 60 - 85 per Cent

Date/Month: 16/05 (Saturday)
Wind: South force 3.
Weather: Sunny periods.
Temp range: 27 - 32 C
R.H. range: 60 - 85 per Cent

Date/Month: 17/05 (Sunday)
Wind: South force 3 to 4.
Weather: Sunny periods.
Temp range: 28 - 32 C
R.H. range: 70 - 90 per Cent

Date/Month: 18/05 (Monday)
Wind: South force 3 to 4.
Weather: Sunny periods and isolated showers.
Temp range: 28 - 32 C
R.H. range: 70 - 90 per Cent

Sea surface temperature at 2 P.M. 09/05/2020 at North Point was 25 degrees C.
Soil temperatures at 7 A.M. 09/05/2020 at Hong Kong Observatory :
0.5 M below surface was 27.6 degrees C
1.0 M below surface was 26.4 degrees C

An anticyclone aloft brought hot weather to southern China yesterday. Locally, it was hot with sunny periods and isolated showers. A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong.

Weather forecast for Hong Kong:
Mainly cloudy with a few showers. Sunny intervals during the day. There will be isolated thunderstorms later. Hot with temperatures ranging between 28 and 32 degrees. Moderate southerly winds.

Outlook: There will be showers and thunderstorms on Monday and Tuesday. The weather will improve gradually in the following couple of days.

We are pleased to announce a major new release with more than 150 new features and improvements!

WYSIWYG Web Builder 7.5 is a major update with more than 50 new features and improvements (compared to version 7.2.1). Our christmas gift to you!

We are pleased to announce a major new release with more than 150 new features and improvements!

WYSIWYG Web Builder 8.5 is a major update with more than 50 new features and improvements (compared to version 8.2.1).

We are pleased to announce a major new release with more than 150 new features and improvements!

WYSIWYG Web Builder 9.1 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 9.2 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 9.3 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 9.4 fixes known problems, adds new features and includes other improvements.

We are pleased to announce a major new release with more than 100 new features and improvements!

WYSIWYG Web Builder 10.1 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 10.2 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 10.3 fixes known problems, adds new features and includes other improvements.

WYSIWYG Web Builder 10.4 fixes known problems, adds new features and includes other improvements.

We are pleased to announce a major new release with more than 150 new features and improvements!

We are pleased to announce a major new release with more than 125 new features and improvements!

Lucía Trilla-Fuertes
Apr 1, 2020; 19:690-700
Research

David Cluet
Apr 1, 2020; 19:701-715
Technological Innovation and Resources

Quentin Perraud
Apr 1, 2020; 19:589-607
Research

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources

Beatriz Rocha
Apr 1, 2020; 19:574-588
Research

Georg H H Borner
Apr 28, 2020; 0:R120.001971v1-mcp.R120.001971
Review

Katrina Meyer
Apr 28, 2020; 0:R120.002034v1-mcp.R120.002034
Review

Bokai Song
Apr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981
Research

Elena Lorente
Apr 7, 2020; 0:RA120.002014v1-mcp.RA120.002014
Research

Daniella H Hock
Apr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076
Research

Michael Plank
Apr 1, 2020; 19:655-671
Research

James A. Wilkins
Apr 13, 2020; 0:RA120.001944v1-mcp.RA120.001944
Research

Eelke P. Béguin
Apr 24, 2020; 0:RA120.001964v1-mcp.RA120.001964
Research

Yunlei Li
Apr 20, 2020; 0:RA120.002017v1-mcp.RA120.002017
Research

Patrick Herr
Apr 1, 2020; 19:608-623
Research

Tatjana Goebel
Apr 16, 2020; 0:RA120.001983v1-mcp.RA120.001983
Research

Adriaan Sticker
Apr 22, 2020; 0:RA119.001624v1-mcp.RA119.001624
Research

Samvel K Gularyan
Apr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986
Research

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research

Guan-Da Syu
Apr 17, 2020; 0:R120.001936v1-mcp.R120.001936
Review

Liye Chen
May 1, 2020; 19:871-883
Research

Élie Lambert
May 1, 2020; 19:808-827
Research

Nora Linscheid
Apr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878
Research

Mona Radwan
Apr 1, 2020; 19:640-654
Research

Yan Zhou Tran
Mar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036
Research

Andreas Linden
Apr 24, 2020; 0:RA120.002028v1-mcp.RA120.002028
Research

Taewook Kang
Apr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882
Research

Lila M. Gierasch
Apr 1, 2020; 19:569-570
Editorial

Xing-Huang Gao
May 1, 2020; 19:852-870
Research

Samuel W Entwisle
Apr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946
Research